CN109307774A - A kind of amino acid, dipeptides or combinations thereof application of the object in terms of colorectal cancer early diagnosis - Google Patents
A kind of amino acid, dipeptides or combinations thereof application of the object in terms of colorectal cancer early diagnosis Download PDFInfo
- Publication number
- CN109307774A CN109307774A CN201811289653.0A CN201811289653A CN109307774A CN 109307774 A CN109307774 A CN 109307774A CN 201811289653 A CN201811289653 A CN 201811289653A CN 109307774 A CN109307774 A CN 109307774A
- Authority
- CN
- China
- Prior art keywords
- metabolic syndrome
- patients
- large bowel
- glutamine
- syndrome patient
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57407—Specifically defined cancers
- G01N33/57446—Specifically defined cancers of stomach or intestine
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/96—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood or serum control standard
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/04—Endocrine or metabolic disorders
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/60—Complex ways of combining multiple protein biomarkers for diagnosis
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Cell Biology (AREA)
- Analytical Chemistry (AREA)
- Biotechnology (AREA)
- Pathology (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Hospice & Palliative Care (AREA)
- Oncology (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
The invention discloses a kind of application of amino acid, dipeptides or combinations thereof the object in terms of colorectal cancer early diagnosis.It is concentrated in the verifying of specific embodiment, isoleucine, tyrosine, phenylalanine, tryptophan or glutamine-leucine individually distinguish the accuracy of health volunteer and PATIENTS WITH LARGE BOWEL as marker 78% or more;Isoleucine, tyrosine, phenylalanine, tryptophan or glutamine-leucine individually distinguish the accuracy of metabolic syndrome patient and PATIENTS WITH LARGE BOWEL as marker 87% or more;The accuracy that tyrosine and glutamine-leucine joint distinguish health volunteer and PATIENTS WITH LARGE BOWEL is up to 97.4%;The accuracy that tyrosine and glutamine-leucine joint distinguish metabolic syndrome patient and PATIENTS WITH LARGE BOWEL is up to 98.2%.It can be seen that above-mentioned amino acid, dipeptides or combinations thereof are high to the diagnosis accuracy of colorectal cancer, diagnosis of colorectal carcinoma kit can be made, the early diagnosis of colorectal cancer is suffered from for Healthy People or metabolic syndrome patient.
Description
Technical field
The invention belongs to disease detection diagnostic fields, are related to the discovery and application of disease diagnosis marker, and in particular to generation
Thank to application of the marker in terms of Metabolic syndrome seeks peace colorectal cancer early diagnosis.
Background technique
Colorectal cancer is common one of malignant tumour, has become one of Chinese three big cancers, illness rate is up to 46.8/10
Ten thousand, and annual new cases are up to ten thousand people of 13-16.If colorectal cancer early detection is timely, 5 years survival rates of patient can reach
90% or more;If early stage fails to find that it is shifted to other organ or tissues in time, survival rate only has 10% or so.Cause
This, colorectal cancer early diagnosis is most important for improving PATIENTS WITH LARGE BOWEL survival rate.
Likelihood ratio ordinary people of the metabolic syndrome patient with colorectal cancer is significantly higher.According to the 73rd U.S.'s gastrointestinal tract year
It can report, the likelihood ratio ordinary people that metabolic syndrome patient suffers from colorectal cancer is high by 75%.A large amount of experimental study discovery, colorectal cancer
Occur and develop and multiple links of metabolic syndrome are all closely related, including fat and diabetes etc..Metabolic syndrome
Refer to that the pathological state of metabolic disorder occurs for the substances such as the protein, fat, carbohydrate of human body, is a complex set of metabolism
Disorder syndrome is the risk factor for leading to diabetes cardiovascular and cerebrovascular disease.The cause of disease of metabolic syndrome is not yet clear at present, main
Be considered polygenes and a variety of environmental interactions as a result, having substantial connection with heredity, immune etc..According to Chinese medical
The diagnostic criteria that meeting diabetology branch suggests, 3 or more had in following 4 can be diagnosed as metabolic syndrome: 1,
Overweight and (or) fat BMI >=25;2, hyperglycemia fasting blood-glucose (FPG) >=6.1mmol/L (110mg/dl) and (or) 2hPG >=
7.8mmol/L (140mg/dl), and (or) made a definite diagnosis diabetes and curer;3, hypertension systolic pressure/diastolic pressure >=140/
90mmHg, and (or) Definite Hypertension and curer;4, blood fat disorder empty stomach blood triglyceride >=1.7mmol/L (150mg/
) and (or) fasting blood HDL-C < 0.9mmol/L (35mg/dl) (male), < 1.0mmol/L (39mg/dl) (female) dl.
The method of diagnosis of colorectal carcinoma is mainly Sigmoidoscope at present, is then confirmed by the method for pathology.Due to colon
Mirror be it is invasive, patient can feel very uncomfortable or even painful.In addition, clinically being gone out using stool occult blood detection to observe enteron aisle
Blood situation, also utilize blood serum designated object such as sugar antigens (CA19-9) and S-CEA (CEA), but CA19-9 and
The maximum defect of CEA is exactly that its specificity and sensitivity are very low, to colorectal cancer without specificity.Therefore, these sides used at present
Method has sizable limitation in the diagnosis of PATIENTS WITH LARGE BOWEL.
Metabolism group is to carry out quantitative analysis to metabolins all in organism and find metabolin and physiological and pathological variation
Relativeness research mode, be the component part of systems biology, be related to life science, analysis science and statistics etc.
Various knowledge, play the role of at present in many fields it is particularly important, new drug development, drug toxicology research and peace
The various fields such as full property evaluation, clinical pathology physiological Study, the early diagnosis of disease, personalized treatment are used widely and are taken
Obtain scientific achievement.
Serum analysis is a kind of clinically common methods for the diagnosis of diseases, because it is easy, quickly, it is economical and relative noninvasive
Advantage and be widely adopted.In recent years, there are many research for colorectal cancer blood serum designated object, also filtered out many marks
Object, but wherein most of markers still lack specificity and sensitivity, and seldom have research to the mark filtered out
Object is verified, because the time cost and economic cost of verifying are very high, not can guarantee the accuracy of result.
It can be seen that in order to improve colorectal cancer early diagnostic rate, there is an urgent need to research and develop higher accuracy rate, sensitivity and
The stronger marker of specificity, and blood serum metabolic marker is with the obvious advantage in terms of diagnosis convenience, economy and minimal invasive.
Summary of the invention
It is an object of the invention to overcome the deficiencies of the prior art and provide metabolic markers to seek peace colorectal cancer in Metabolic syndrome
Early diagnose the application of aspect.The purpose is achieved through the following technical solutions:
Scheme 1: amino acid, dipeptides or combinations thereof object diagnose colorectal cancer as marker
A kind of amino acid, dipeptides or combinations thereof object are suffered from preparation for early diagnosing Healthy People or metabolic syndrome patient
Application in terms of the diagnostic kit of colorectal cancer;The amino acid is isoleucine, tyrosine, phenylalanine or tryptophan, institute
Stating dipeptides is glutamine-leucine.
Preferably, the standard items containing amino acid, dipeptides or combinations thereof object in diagnostic kit;The amino acid is different bright
Propylhomoserin, tyrosine, phenylalanine or tryptophan, dipeptides are glutamine-leucine.
Preferably, the standard items in diagnostic kit also containing internal standard compound.
It is concentrated in the verifying of specific embodiment, it is bright with isoleucine, tyrosine, phenylalanine, tryptophan or glutamine-
Propylhomoserin individually distinguish the best cut-off value of health volunteer and PATIENTS WITH LARGE BOWEL patient be diagnostic threshold to health volunteer and
The serum sample of PATIENTS WITH LARGE BOWEL is predicted that accuracy is 78% or more;With isoleucine, tyrosine, phenylalanine, color ammonia
It is to examine that acid or glutamine-leucine, which individually distinguish metabolic syndrome patient and the best cut-off value of PATIENTS WITH LARGE BOWEL patient,
Disconnected threshold value predicts that accuracy is 87% or more to the serum sample of metabolic syndrome patient and PATIENTS WITH LARGE BOWEL;Tyrosine
The accuracy for combining differentiation health volunteer and PATIENTS WITH LARGE BOWEL with glutamine-leucine is up to 97.4%;Tyrosine and paddy
The accuracy that glutamine-leucine joint distinguishes metabolic syndrome patient and PATIENTS WITH LARGE BOWEL is up to 98.2%.
Scheme 2: p-Coumaric Acid or phosphatidyl-ethanolamine PE (18:2 (9Z, 12Z)/P-18:0) are diagnosed as marker
Colorectal cancer
P-Coumaric Acid or phosphatidyl-ethanolamine PE (18:2 (9Z, 12Z)/P-18:0) are strong for early diagnosing in preparation
Health people or metabolic syndrome patient suffer from the application in terms of the diagnostic kit of colorectal cancer.
Preferably, p-Coumaric Acid or phosphatidyl-ethanolamine PE (18:2 (9Z, 12Z)/P-18:0) are contained in kit
Standard items.
Preferably, the standard items in kit also containing internal standard compound.
It is concentrated in the verifying of specific embodiment, with p-Coumaric Acid or phosphatidyl-ethanolamine PE (18:2 (9Z, 12Z)/P-
The best cut-off value for 18:0) individually distinguishing health volunteer and PATIENTS WITH LARGE BOWEL patient is diagnostic threshold to health volunteer
It is predicted with the serum sample of PATIENTS WITH LARGE BOWEL, accuracy is respectively up to 85.9%, 98.5%;With p-Coumaric Acid or phosphatide
The independent differentiation metabolic syndrome patient of acyl ethanol amine PE (18:2 (9Z, 12Z)/P-18:0) is best with PATIENTS WITH LARGE BOWEL patient's
Cut-off value is that diagnostic threshold predicts the serum sample of metabolic syndrome patient and PATIENTS WITH LARGE BOWEL, accuracy difference
Up to 92.3%, 99.0%.
Scheme 3: multiple metabolic markers combination diagnosis metabolic syndrome patients
One group of metabolic markers is preparing for early diagnosing in terms of Healthy People suffers from the diagnostic kit of metabolic syndrome
Application;The metabolic markers include at least glutamine-leucine and phosphatidyl-ethanolamine PE (18:2 (9Z, 12Z)/P-
It 18:0), further include tyrosine or phenylalanine.
Preferably, metabolic markers include at least glutamine-leucine and phosphatidyl-ethanolamine PE (18:2 (9Z,
12Z)/P-18:0), it further include tyrosine and phenylalanine.
Preferably, the metabolic markers further include isoleucine, tryptophan and p-Coumaric Acid.
Preferably, the standard items of the metabolic markers are contained in the diagnostic kit.
Preferably, the standard items in the diagnostic kit also containing internal standard compound.
It is concentrated in the verifying of specific embodiment, tyrosine, phosphatidyl-ethanolamine PE (18:2 (9Z, 12Z)/P-18:0) and paddy
Glutamine-leucine joint distinguishes the accuracy of health volunteer and metabolic syndrome patient up to 80.5%;Phenylalanine, paddy ammonia
Amide-leucine and phosphatidyl-ethanolamine PE (18:2 (9Z, 12Z)/P-18:0) joint distinguish health volunteer and Metabolic syndrome
The accuracy of patient is levied up to 82.6%;Isoleucine, tyrosine, phenylalanine, tryptophan, glutamine-leucine, to hydroxyl
Cinnamic acid and phosphatidyl-ethanolamine PE (18:2 (9Z, 12Z)/P-18:0) seven target metabolites joint distinguish health volunteers and
The accuracy of metabolic syndrome patient, accuracy 83.8%.
Detailed description of the invention
Fig. 1 is that isoleucine individually diagnoses the ROC song for distinguishing health volunteer, metabolic syndrome patient or PATIENTS WITH LARGE BOWEL
Line, in which: A represents PATIENTS WITH LARGE BOWEL VS health volunteer, and B represents metabolic syndrome patient VS health volunteer, and C represents large intestine
Cancer patient VS metabolic syndrome patient;
Fig. 2 is that tyrosine individually diagnoses the ROC song for distinguishing health volunteer, metabolic syndrome patient or PATIENTS WITH LARGE BOWEL
Line, in which: A represents PATIENTS WITH LARGE BOWEL VS health volunteer, and B represents metabolic syndrome patient VS health volunteer, and C represents large intestine
Cancer patient VS metabolic syndrome patient;
Fig. 3 is that phenylalanine individually diagnoses the ROC song for distinguishing health volunteer, metabolic syndrome patient or PATIENTS WITH LARGE BOWEL
Line, in which: A represents PATIENTS WITH LARGE BOWEL VS health volunteer, and B represents metabolic syndrome patient VS health volunteer, and C represents large intestine
Cancer patient VS metabolic syndrome patient;
Fig. 4 is that the independent diagnostic region of tryptophan divides the ROC of health volunteer, metabolic syndrome patient or PATIENTS WITH LARGE BOWEL bent
Line, in which: A represents PATIENTS WITH LARGE BOWEL VS health volunteer, and B represents metabolic syndrome patient VS health volunteer, and C represents large intestine
Cancer patient VS metabolic syndrome patient;
Fig. 5 is that glutamine-leucine individually diagnoses differentiation health volunteer, metabolic syndrome patient or PATIENTS WITH LARGE BOWEL
ROC curve, in which: A represents PATIENTS WITH LARGE BOWEL VS health volunteer, and B represents metabolic syndrome patient VS health volunteer, C
Represent PATIENTS WITH LARGE BOWEL VS metabolic syndrome patient;
Fig. 6 is that p-Coumaric Acid individually diagnoses differentiation health volunteer, metabolic syndrome patient or PATIENTS WITH LARGE BOWEL
ROC curve, in which: A represents PATIENTS WITH LARGE BOWEL VS health volunteer, and B represents metabolic syndrome patient VS health volunteer, C generation
Table PATIENTS WITH LARGE BOWEL VS metabolic syndrome patient;
Fig. 7 is that phosphatidyl-ethanolamine PE (18:2 (9Z, 12Z)/P-18:0) individually diagnosis differentiation health volunteer, metabolism are comprehensive
The ROC curve of simulator sickness patient or PATIENTS WITH LARGE BOWEL, in which: A represents PATIENTS WITH LARGE BOWEL VS health volunteer, and B represents Metabolic syndrome
Patient VS health volunteer is levied, C represents PATIENTS WITH LARGE BOWEL VS metabolic syndrome patient;
Fig. 8 is the ROC curve that tyrosine and glutamine-leucine joint distinguish health volunteer VS PATIENTS WITH LARGE BOWEL;
Fig. 9 is the ROC song that tyrosine and glutamine-leucine joint distinguish metabolic syndrome patient VS PATIENTS WITH LARGE BOWEL
Line;
Figure 10 is tyrosine, glutamine-leucine and phosphatidyl-ethanolamine PE (18:2 (9Z, 12Z)/P-18:0) joint
Distinguish the ROC curve of health volunteer VS metabolic syndrome patient;
Figure 11 is phenylalanine, glutamine-leucine and phosphatidyl-ethanolamine PE (18:2 (9Z, 12Z)/P-18:0) connection
Close the ROC curve for distinguishing health volunteer VS metabolic syndrome patient;
Figure 12 is the ROC curve that seven target metabolite joints distinguish health volunteer VS PATIENTS WITH LARGE BOWEL;
Figure 13 is the ROC curve that seven target metabolite joints distinguish metabolic syndrome patient VS PATIENTS WITH LARGE BOWEL;
Figure 14 is the ROC curve that seven target metabolite joints distinguish health volunteer VS metabolic syndrome patient.
Specific embodiment
It is specific with reference to the accompanying drawings and examples to introduce essentiality content of the present invention, but guarantor of the invention is not limited with this
Protect range.
Embodiment 1: the diagnosis of health volunteer, metabolic syndrome patient or PATIENTS WITH LARGE BOWEL is distinguished in target metabolite diagnosis
Efficiency
One, experiment sample
Training set sample: Xiaoshan area and Shaoyifu Hospital Attached to Zhejiang Univ. Medical College are collected, according to stringent screening
With exclusion criteria by age and matched 120 health volunteers of gender, 120 metabolic syndrome patients and 120 large intestines
Cancer patient.
Verifying collection sample: collecting Xiaoshan area, Shaoyifu Hospital Attached to Zhejiang Univ. Medical College and Taizhou tumour hospital,
According to 580 health volunteers of stringent screening and exclusion criteria, 577 metabolic syndrome patients, 437 colorectal cancers are suffered from
Person.
The inclusion criteria of health volunteer, metabolic syndrome patient and PATIENTS WITH LARGE BOWEL are as follows:
Normal volunteer: absent cardiovascular, breathing, liver, kidney, gastrointestinal tract, endocrine, blood, spirit or nerveous system
Disease of uniting and above-mentioned disease medical history, without acute or chronic disease.Medicine-less allergy history, clinical labororatory checks knot when screening
Fruit is in normal term of reference.
Metabolic syndrome patient: the diagnostic criteria (2004) suggested according to diabetology branch of Chinese Medical Association has
3 in following 4 or all it is diagnosed as metabolic syndrome patient: 1, overweight and (or) fat BMI >=25;2, hyperglycemia is empty
Abdomen blood glucose (FPG) >=6.1mmol/L (110mg/dl) and (or) 2hPG >=7.8mmol/L (140mg/dl), and (or) made a definite diagnosis
Diabetes and curer;3, hypertension systolic pressure/diastolic pressure >=140/90mmHg, and (or) Definite Hypertension and curer;
4, blood fat disorder empty stomach blood triglyceride>=1.7mmol/L (150mg/dl) and (or) fasting blood HDL-C<0.9mmol/L
(35mg/dl) (male), < 1.0mmol/L (39mg/dl) (female).
Colorectal cancer: determining by colonoscopy and be judged as that colon cancer or the carcinoma of the rectum and preparing receives the trouble of surgery for colorectal carcinoma
Person.
Main agents: methanol and acetonitrile (UPLC is pure) are purchased from merk company of the U.S., and chromatographic grade formic acid and ammonium acetate are purchased from beauty
ROE company of state;Deionized water is prepared by the MIlli-Q ultrapure water system of U.S. Mi Libo (Millipore) company;Standard items packet
It includes isoleucine, tyrosine, phenylalanine, tryptophan, p-Coumaric Acid and is purchased from Sigma-Aldrich, paddy ammonia
Amide-leucine is synthesized by Nanjing Tai Ye Biotechnology Co., Ltd.It is raw that internal standard L-2- chlorophenylalanine is purchased from Shanghai Mike woods
Change Science and Technology Ltd., Ketoprofen is purchased from National Institute for Food and Drugs Control.
Two, experimental method
1, the acquisition and storage of serum sample
Acquisition patient's early morning empty stomach peripheral blood simultaneously places it in the test tube without anti-coagulants, is aggregated naturally at room temperature
30-60min is waited for blood to solidify, and is centrifuged 10min with the speed of 2000rpm, the careful limpid sera liquid in upper layer of drawing is in sterile jelly
It is spare that -80 DEG C of refrigerator storages are put into main pipe, after label.
2, UPLC-Q/TOF-MS measures the relative amount of target metabolite in serum
Detecting instrument: 1290 high performance liquid chromatograph of Agilent, the combination of 6545 quadrupole time-of-flight mass spec-trometry of Agilent
Instrument.
Chromatographic condition: chromatographic column: Waters BEH C8 (100mm × 2.1mm I.D., 1.7 μm);Cation mobile phase second
Nitrile (B)-water (A) solution (contains 0.1% formic acid);Anion mobile phase methanol (B)-water (A) solution (acetic acid containing 10mmol/L
Ammonium);Flow velocity: 0.4mL/min;Column temperature: 50 DEG C.Mobile phase ratio: 0-1min, 5%B;1-4min, 5%-30%B;4-9min,
30%-90%B;9-10min, 90%-100%B;10-12min, 100%B.Runing time is 12 minutes, and rear runing time is 3
Minute.
Mass Spectrometry Conditions: fragment voltage: 100V;Atomization gas: 35psig;Capillary voltage: 3500V;Flows of dry gases:
10L/min;Dry gas temperature: 300 DEG C.
Sample process: taking the serum sample of 50 μ L, the 150 μ L of methanol of 3 times of amounts is then added, vortex 30s is mixed, mixed
It is put into supercentrifuge and is centrifuged after even, 10min is centrifuged under the conditions of 13000rpm.The supernatant drawn after being centrifuged is each
75 μ L are respectively put into 2 1.5ml centrifuge tubes, are dried up supernatant using nitrogen evaporator, are utilized respectively again containing in after drying
The methanol of standard liquid (L-2- chlorophenylalanine) redissolves 100 μ L of liquid or the methanol containing internal standard solution (Ketoprofen) redissolve 100 μ L of liquid into
Row redissolve, L-2- chlorophenylalanine, Ketoprofen final concentration be respectively 100ng/mL, 1 μ g/mL, respectively as negative ions mould
Formula detects sample.The 30s that is vortexed again after redissolution is mixed, and is put into supercentrifuge and is centrifuged after mixing, 13000rpm
Under the conditions of be centrifuged 10min, draw the supernatant after centrifugation, after supernatant be placed in sample introduction in liquid matter bottle measure (sample introduction
Amount be 1 μ L), calculate each target metabolite isoleucine, tyrosine, phenylalanine, tryptophan, glutamine-leucine, to hydroxyl
The ratio conduct of base cinnamic acid, the peak area of phosphatidyl-ethanolamine PE (18:2 (9Z, 12Z)/P-18:0) and interior target peak area
The relative amount of the metabolin.
3, data processing method
In training set, the relative amount of target metabolite is compared using orthogonal offset minimum binary discriminance (OPLS-DA)
It whether there is difference in the serum of Healthy People, metabolic syndrome, PATIENTS WITH LARGE BOWEL, be that difference has statistics with VIP>1 and p<0.05
Meaning is learned, and establishes the ROC curve of single target metabolin, area (AUC) and 95% credibility interval under calculated curve;For more
A target metabolite establishes regression equation with Logistic recurrence, generates one group of new variables logit [p], to the new variables into
The analysis of row ROC curve.Verifying is concentrated, the best cut-off value obtained using ROC curve as threshold calculations single target metabolin or
It combines the diagnosis accuracy for colorectal cancer, metabolic syndrome.
Three, experimental result
1, level difference of the target metabolite in health volunteer, metabolic syndrome patient and Serum In Patients With Colorectal Carcinoma
In training set, and health volunteer's ratio, metabolic syndrome patient's serum paraoxonase acyl ethanol amine PE (18:2 (9Z,
12Z)/P-18:0) relative amount significantly lower, the bright ammonia of isoleucine, tyrosine, phenylalanine, tryptophan, glutamine-
Sour, p-Coumaric Acid relative amount significantly raises;Compared with health volunteer, above-mentioned 7 mesh in Serum In Patients With Colorectal Carcinoma
Mark metabolin is significantly lowered;Compared with metabolic syndrome patient, above-mentioned 7 target metabolites are aobvious in Serum In Patients With Colorectal Carcinoma
It writes and lowers.
2, target metabolite individually diagnoses the ROC song for distinguishing health volunteer, metabolic syndrome patient or PATIENTS WITH LARGE BOWEL
Line
The principle of ROC curve evaluation assessment:
The Basic Evaluation index of diagnostic test has susceptibility, specificity etc., comprehensive evaluation index have Youden index, ROC,
AUC etc..Evaluation for diagnostic test, it is necessary first to the true group of sample to be tested is known by goldstandard.For down payment mark
Accurately fixed disease group (the Bone of Breast Cancer transfer group being equivalent in the present invention) and healthy group (are equivalent to the breast cancer in the present invention
Non- transfer group), following situation can be divided into using the result that diagnostic test detects:
Positive (True Positive, TP);Diagnostic test test positive (consistent with goldstandard result);
Negative (True Negative, TN);Diagnostic test is detected as negative (consistent with goldstandard result);
False positive (False Positive, FP): diagnostic test test positive (inconsistent with goldstandard result);
False negative (False Negative, FN): diagnostic test is detected as negative (inconsistent with goldstandard result).
It can be indicated with following table:
Susceptibility=A/ (A+C) of diagnostic test;Specificity=D/ (B+D) of diagnostic test.By susceptibility and specifically
Property is it can be concluded that diagnosis sensitivity level and specific degree of the diagnostic test relative to goldstandard.Disease example is examined in the representative of susceptibility height
Break few for negative number, rate of missed diagnosis is low;The number that healthy example is diagnosed as the positive by specific high representative is few, and misdiagnosis rate is low.
The curve that ROC curve is based on above-mentioned susceptibility and specificity is drawn out.With diagnosis possible in diagnostic test
Dividing value calculates corresponding susceptibility and specificity as diagnostic points, according to above table.Then, using susceptibility as ordinate,
1- specificity is abscissa, the susceptibility of each point when each diagnostic points and specificity point is marked in coordinate diagram, connection coordinate point
Smoothed curve is obtained, which is ROC curve.Diagnostic points are arranged much closeer, and obtained ROC curve is more smooth.
ROC curve is using each testing result as possible diagnosis dividing value, and the size of area under the curve AUC shows
The size of diagnostic test accuracy.Intrinsic accuracy index of the area AUC as diagnostic test Authentic Assessment under ROC curve
It has been be commonly recognized that, when AUC is 0.5, i.e., without diagnostic significance;AUC indicates that accuracy rate of diagnosis is lower at 0.5~0.7;AUC exists
When 0.7~0.9, indicate that diagnostic accuracy is medium;When AUC > 0.9, indicate that diagnosis has higher accuracy.
Isoleucine, tyrosine, phenylalanine, tryptophan, glutamine-leucine, p-Coumaric Acid, phosphatidyl second
Individually health volunteer, metabolic syndrome patient or PATIENTS WITH LARGE BOWEL are distinguished in diagnosis to hydramine PE (18:2 (9Z, 12Z)/P-18:0)
ROC curve result as shown in table 1~3 and Fig. 1~7.A represents PATIENTS WITH LARGE BOWEL VS health volunteer in Fig. 1~7, and B represents generation
Thank to syndrome patient VS health volunteer, C represents PATIENTS WITH LARGE BOWEL VS metabolic syndrome patient.
1 target metabolite of table individually diagnoses the ROC curve for distinguishing PATIENTS WITH LARGE BOWEL VS health volunteer
2 target metabolite of table individually diagnoses the ROC curve for distinguishing PATIENTS WITH LARGE BOWEL VS metabolic syndrome patient
3 target metabolite of table individually diagnoses the ROC curve for distinguishing metabolic syndrome patient VS health volunteer
ROC curve the result shows that, isoleucine, tyrosine, phenylalanine, tryptophan, glutamine-leucine, to hydroxyl
Individually diagnosis differentiation PATIENTS WITH LARGE BOWEL VS health is tested by base cinnamic acid, phosphatidyl-ethanolamine PE (18:2 (9Z, 12Z)/P-18:0)
Person or PATIENTS WITH LARGE BOWEL VS metabolic syndrome patient accuracy all with higher (AUC is 0.9 or more);Isoleucine, junket
Propylhomoserin, phenylalanine, tryptophan, glutamine-leucine, p-Coumaric Acid, phosphatidyl-ethanolamine PE (18:2 (9Z,
12Z)/P-18:0) individually diagnosis distinguish metabolic syndrome patient VS health volunteer and all there is medium accuracy (AUC exists
0.7~0.9).
It can be seen that the bright ammonia of isoleucine, tyrosine, phenylalanine, tryptophan, glutamine-from ROC curve result
Acid, p-Coumaric Acid, phosphatidyl-ethanolamine PE (18:2 (9Z, 12Z)/P-18:0) are individually tested to PATIENTS WITH LARGE BOWEL VS health
Person or PATIENTS WITH LARGE BOWEL VS metabolic syndrome patient have had stronger diagnosis separating capacity, further according to ROC curve
Coordinate calculates dimension mounting index=specificity+sensitivity -1, when tieing up mounting index maximum value corresponding metabolin relative amount be can be into
The best cut-off value of PATIENTS WITH LARGE BOWEL VS health volunteer or PATIENTS WITH LARGE BOWEL VS metabolic syndrome patient are distinguished in row diagnosis,
As shown in table 4.
4 target metabolite of table individually distinguishes PATIENTS WITH LARGE BOWEL and Healthy People or the best cut-off of metabolic syndrome patient
Value
3, the ROC that multiple target metabolite joints distinguish health volunteer, metabolic syndrome patient or PATIENTS WITH LARGE BOWEL is bent
Line
3.1 tyrosine and glutamine-leucine joint distinguish health volunteer VS PATIENTS WITH LARGE BOWEL
(X is set as independent variable using the relative amount of tyrosine and glutamine-leucine in training set sample1=junket ammonia
Sour relative amount, X2=glutamine-leucine relative amount), using group (i.e. health volunteer and PATIENTS WITH LARGE BOWEL) as
Dependent variable, to the relative amount of tyrosine and glutamine-leucine in health volunteer and Serum In Patients With Colorectal Carcinoma sample
Dualistic logistic regression is carried out, dualistic logistic regression equation: logit [p]=11.35-5.353X is obtained1-75.46X2;Again by each blood
The relative amount of tyrosine and glutamine-leucine substitutes into the dualistic logistic regression equation in final proof sheet, can be obtained each
The regressand value logit [p] of serum sample, using possible regressand value logit [p] as diagnostic points, meter sensitivity and specificity,
ROC curve (such as Fig. 8) is drawn accordingly, AUC 0.983, accuracy with higher.Coordinate according to ROC curve calculates dimension and steps on
Index=specificity+sensitivity -1, when tieing up mounting index maximum value corresponding logit [p] value be can be carried out diagnosis distinguish health by
The best cut-off value 0.468 of examination person's VS PATIENTS WITH LARGE BOWEL.
3.2 tyrosine and glutamine-leucine joint distinguish metabolic syndrome patient VS PATIENTS WITH LARGE BOWEL
(X is set as independent variable using the relative amount of tyrosine and glutamine-leucine in training set sample1=junket ammonia
Sour relative amount, X2=glutamine-leucine relative amount), with group (i.e. metabolic syndrome patient and PATIENTS WITH LARGE BOWEL)
As dependent variable, to tyrosine and glutamine-leucine in metabolic syndrome patient and Serum In Patients With Colorectal Carcinoma sample
Relative amount carries out dualistic logistic regression, obtains dualistic logistic regression equation: logit [p]=26.471-12.62X1-
126.2X2;The relative amount of tyrosine and glutamine-leucine in each serum sample is substituted into the dualistic logistic regression side again
The regressand value logit [p] of each serum sample can be obtained in journey, using possible regressand value logit [p] as diagnostic points, calculates
Sensitivity and specificity draw ROC curve (such as Fig. 9) accordingly, AUC 0.995, accuracy with higher.According to ROC curve
Coordinate calculate dimension mounting index=specificity+sensitivity -1, corresponding logit [p] value is that can be carried out when tieing up mounting index maximum value
The best cut-off value 0.657 of metabolic syndrome patient VS PATIENTS WITH LARGE BOWEL is distinguished in diagnosis.
3.3 tyrosine, glutamine-leucine and phosphatidyl-ethanolamine PE (18:2 (9Z, 12Z)/P-18:0) association area
Divide health volunteer VS metabolic syndrome patient
With tyrosine, glutamine-leucine and phosphatidyl-ethanolamine PE (18:2 (9Z, 12Z)/P- in training set sample
Relative amount 18:0) (sets X as independent variable1=tyrosine relative amount, X2=glutamine-leucine relative amount, X3
=phosphatidyl-ethanolamine PE (18:2 (9Z, 12Z)/P-18:0) relative amount), with group (i.e. health volunteer and Metabolic syndrome
Levy patient) be used as dependent variable, to tyrosine, glutamine-leucine and phosphatidyl-ethanolamine PE (18:2 (9Z, 12Z)/P-18:
0) relative amount in health volunteer and metabolic syndrome patient's serum sample carries out dualistic logistic regression, obtains binary and patrols
Collect regression equation: logit [p]=- 3.868+3.117X1+5.486X2-11.79X3;Again by tyrosine, paddy in each serum sample
The relative amount of glutamine-leucine and phosphatidyl-ethanolamine PE (18:2 (9Z, 12Z)/P-18:0) substitute into the binary logic and return
Return equation, the regressand value logit [p] of each serum sample can be obtained, using possible regressand value logit [p] as diagnostic points,
Meter sensitivity and specificity draw ROC curve (such as Figure 10) accordingly, AUC 0.882, accuracy with higher.According to
The coordinate of ROC curve calculates dimension mounting index=specificity+sensitivity -1, and corresponding logit [p] value is when tieing up mounting index maximum value
It can be carried out the best cut-off value 0.509 that health volunteer VS metabolic syndrome patient is distinguished in diagnosis.
3.4 phenylalanines, glutamine-leucine and phosphatidyl-ethanolamine PE (18:2 (9Z, 12Z)/P-18:0) joint
Distinguish health volunteer VS metabolic syndrome patient
With phenylalanine in training set sample, glutamine-leucine and phosphatidyl-ethanolamine PE (18:2 (9Z, 12Z)/
P-18:0 relative amount) (sets X as independent variable1=phenylalanine relative amount, X2=glutamine-leucine is opposite to be contained
Amount, X3=phosphatidyl-ethanolamine PE (18:2 (9Z, 12Z)/P-18:0) relative amount), with group (i.e. health volunteer and metabolism
Syndrome patient) be used as dependent variable, to phenylalanine, glutamine-leucine and phosphatidyl-ethanolamine PE (18:2 (9Z,
12Z)/P-18:0) relative amount in health volunteer and metabolic syndrome patient's serum sample carries out dualistic logistic regression,
Obtain dualistic logistic regression equation: logit [p]=- 3.067+2.430X1+6.270X2-12.20X3;It again will be in each serum sample
The relative amount of phenylalanine, glutamine-leucine and phosphatidyl-ethanolamine PE (18:2 (9Z, 12Z)/P-18:0) substitutes into should
The regressand value logit [p] of each serum sample can be obtained in dualistic logistic regression equation, with possible regressand value logit [p]
As diagnostic points, meter sensitivity and specificity draw ROC curve (such as Figure 11) accordingly, AUC 0.874, standard with higher
True property.Coordinate according to ROC curve calculates dimension mounting index=specificity+sensitivity -1, ties up corresponding when mounting index maximum value
Logit [p] value is the best cut-off value 0.522 that can be carried out diagnosis and distinguish health volunteer VS metabolic syndrome patient.
3.5 7 target metabolite joints distinguish health volunteer VS PATIENTS WITH LARGE BOWEL
(X is set as independent variable using the relative amount of seven target metabolites in training set sample1=isoleucine is opposite to be contained
Amount, X2=tyrosine relative amount, X3=phenylalanine relative amount, X4=tryptophan relative amount, X5=glutamine-is bright
Propylhomoserin relative amount, X6=p-Coumaric Acid relative amount, X7=phosphatidyl-ethanolamine PE (18:2 (9Z, 12Z)/P-18:0)
Relative amount), using group (i.e. health volunteer and PATIENTS WITH LARGE BOWEL) as dependent variable, to seven target metabolites health by
Relative amount in examination person and Serum In Patients With Colorectal Carcinoma sample carries out dualistic logistic regression, obtains dualistic logistic regression equation:
Logit [p]=50.41+28.17X1-42.75X2+136.71X3-26.86X4-149.81X5-142.56X6-126.95X7;Again
The relative amount of seven target metabolites in each serum sample is substituted into the dualistic logistic regression equation, each serum can be obtained
The regressand value logit [p] of sample, using possible regressand value logit [p] as diagnostic points, meter sensitivity and specificity, accordingly
It draws ROC curve (such as Figure 12), AUC 1.000, there is high accuracy.Coordinate calculating dimension mounting index according to ROC curve=
Specificity+sensitivity -1, corresponding logit [p] value is that can be carried out diagnosis to distinguish health volunteer VS when tieing up mounting index maximum value
The best cut-off value 0.5 of PATIENTS WITH LARGE BOWEL.
3.6 7 target metabolite joints distinguish metabolic syndrome patient VS PATIENTS WITH LARGE BOWEL
(X is set as independent variable using the relative amount of seven target metabolites in training set sample1=isoleucine is opposite to be contained
Amount, X2=tyrosine relative amount, X3=phenylalanine relative amount, X4=tryptophan relative amount, X5=glutamine-is bright
Propylhomoserin relative amount, X6=p-Coumaric Acid relative amount, X7=phosphatidyl-ethanolamine PE (18:2 (9Z, 12Z)/P-18:0)
Relative amount), using group (i.e. metabolic syndrome patient and PATIENTS WITH LARGE BOWEL) as dependent variable, to seven target metabolites in generation
The relative amount thanked in syndrome patient and Serum In Patients With Colorectal Carcinoma sample carries out dualistic logistic regression, obtains dualistic logistic regression
Equation: logit [p]=40.50+2.210X1+122.47X2-218.87X3-12.71X4-63.13X5-74.26X6-
169.44X7;The relative amount of seven target metabolites in each serum sample is substituted into the dualistic logistic regression equation again
The regressand value logit [p] of each serum sample is obtained, using possible regressand value logit [p] as diagnostic points, meter sensitivity
And specificity, ROC curve (such as Figure 13) is drawn accordingly, AUC 1.000, accuracy with higher.Seat according to ROC curve
Mark calculates dimension mounting index=specificity+sensitivity -1, and corresponding logit [p] value is that can be carried out diagnosis when tieing up mounting index maximum value
Distinguish the best cut-off value 0.5 of metabolic syndrome patient VS PATIENTS WITH LARGE BOWEL.
3.7 7 target metabolite joints distinguish health volunteer VS metabolic syndrome patient
(X is set as independent variable using the relative amount of seven target metabolites in training set sample1=isoleucine is opposite to be contained
Amount, X2=tyrosine relative amount, X3=phenylalanine relative amount, X4=tryptophan relative amount, X5=glutamine-is bright
Propylhomoserin relative amount, X6=p-Coumaric Acid relative amount, X7=phosphatidyl-ethanolamine PE (18:2 (9Z, 12Z)/P-18:0)
Relative amount), using group (i.e. health volunteer and metabolic syndrome patient) as dependent variable, to seven target metabolites strong
Relative amount in health subject and metabolic syndrome patient's serum sample carries out dualistic logistic regression, obtains dualistic logistic regression
Equation: logit [p]=- 3.977+3.000X1-5.726X2+15.08X3-1.057X4-0.980X5+3.501X6-11.32X7;
The relative amount of seven target metabolites in each serum sample is substituted into the dualistic logistic regression equation again, each blood can be obtained
The regressand value logit [p] of final proof sheet, using possible regressand value logit [p] as diagnostic points, meter sensitivity and specificity, according to
This draws ROC curve (such as Figure 14), AUC 0.895, accuracy with higher.Coordinate according to ROC curve calculates dimension and steps on finger
Number=specificity+sensitivity -1, corresponding logit [p] value is tested to can be carried out diagnosis differentiation health when tieing up mounting index maximum value
The best cut-off value 0.510 of person VS metabolic syndrome patient.
4, verifying single target metabolin distinguishes the accuracy of health volunteer VS PATIENTS WITH LARGE BOWEL
Verifying concentrate, with isoleucine, tyrosine, phenylalanine, tryptophan, glutamine-leucine, to hydroxyl meat
Cinnamic acid or phosphatidyl-ethanolamine PE (18:2 (9Z, 12Z)/P-18:0) individually distinguish health volunteer and PATIENTS WITH LARGE BOWEL patient's
Best cut-off value is that diagnostic threshold predicts the serum sample of health volunteer and PATIENTS WITH LARGE BOWEL, in serum sample
The relative amount of the target metabolite is predicted as health volunteer higher than diagnostic threshold, lower than being predicted as greatly for the diagnostic threshold
Patients with bowel cancer, with predict correct sample number divided by total number of samples (580+437=1017) be the target metabolite distinguish it is strong
The accuracy of health subject's VS PATIENTS WITH LARGE BOWEL.The differentiation accuracy of each target metabolite is as shown in table 5.
The accuracy of 5 single target metabolin of table differentiation health volunteer VS PATIENTS WITH LARGE BOWEL
As a result as it can be seen that the accuracy of each single target metabolin differentiation health volunteer VS PATIENTS WITH LARGE BOWEL is higher.
5, verifying single target metabolin distinguishes the accuracy of metabolic syndrome patient VS PATIENTS WITH LARGE BOWEL
Verifying concentrate, with isoleucine, tyrosine, phenylalanine, tryptophan, glutamine-leucine, to hydroxyl meat
Cinnamic acid or phosphatidyl-ethanolamine PE (18:2 (9Z, 12Z)/P-18:0) individually distinguish metabolic syndrome patient and PATIENTS WITH LARGE BOWEL is suffered from
The best cut-off value of person is that diagnostic threshold predicts the serum sample of metabolic syndrome patient and PATIENTS WITH LARGE BOWEL, blood
The relative amount of the target metabolite is predicted as metabolic syndrome patient higher than diagnostic threshold in final proof sheet, is lower than the diagnosis threshold
Value is predicted as PATIENTS WITH LARGE BOWEL, to predict that correct sample number divided by total number of samples (577+437=1014) is the target
The accuracy of metabolin differentiation metabolic syndrome patient VS PATIENTS WITH LARGE BOWEL.The differentiation accuracy of each target metabolite such as 6 institute of table
Show.
The accuracy of 6 single target metabolin of table differentiation metabolic syndrome patient VS PATIENTS WITH LARGE BOWEL
As a result as it can be seen that the accuracy of each single target metabolin differentiation metabolic syndrome patient VS PATIENTS WITH LARGE BOWEL is higher.
6, the standard that multiple target metabolite joints distinguish health volunteer, metabolic syndrome patient or PATIENTS WITH LARGE BOWEL is verified
Exactness
6.1 tyrosine and glutamine-leucine joint distinguish the accuracy of health volunteer VS PATIENTS WITH LARGE BOWEL
It concentrates in verifying, by tyrosine in health volunteer and Serum In Patients With Colorectal Carcinoma sample, glutamine-leucine
Relative amount substitutes into tyrosine and glutamine-leucine joint distinguishes the binary logic time of health volunteer VS PATIENTS WITH LARGE BOWEL
Return equation, the regressand value logit [p] of each sample is calculated, is distinguished with above-mentioned tyrosine and glutamine-leucine joint
The best cut-off value of health volunteer's VS PATIENTS WITH LARGE BOWEL is diagnostic threshold, and logit [p] is higher than the prediction of the diagnostic threshold
For health volunteer, it is predicted as PATIENTS WITH LARGE BOWEL lower than the diagnostic threshold, to predict correct sample number divided by total number of samples
(580+437=1017) is the standard that tyrosine and glutamine-leucine joint distinguish health volunteer VS PATIENTS WITH LARGE BOWEL
Exactness, accuracy 97.4%.
6.2 tyrosine and glutamine-leucine joint distinguish the accuracy of metabolic syndrome patient VS PATIENTS WITH LARGE BOWEL
It is concentrated in verifying, by tyrosine, the bright ammonia of glutamine-in metabolic syndrome patient and Serum In Patients With Colorectal Carcinoma sample
The relative amount of acid substitutes into tyrosine and glutamine-leucine joint distinguishes the two of metabolic syndrome patient VS PATIENTS WITH LARGE BOWEL
The regressand value logit [p] of each sample is calculated, with above-mentioned tyrosine and glutamine-leucine in metalogic regression equation
The best cut-off value that joint distinguishes metabolic syndrome patient VS PATIENTS WITH LARGE BOWEL is diagnostic threshold, and logit [p] is examined higher than this
Disconnected threshold value is predicted as metabolic syndrome patient, PATIENTS WITH LARGE BOWEL is predicted as lower than the diagnostic threshold, to predict correct sample
This number is that tyrosine and glutamine-leucine joint distinguish metabolic syndrome divided by total number of samples (577+437=1014)
The accuracy of patient's VS PATIENTS WITH LARGE BOWEL, accuracy 98.2%.
6.3 tyrosine, glutamine-leucine and phosphatidyl-ethanolamine PE (18:2 (9Z, 12Z)/P-18:0) association area
Divide the accuracy of health volunteer VS metabolic syndrome patient
It is concentrated in verifying, by tyrosine, the bright ammonia of glutamine-in health volunteer and metabolic syndrome patient's serum sample
Acid and phosphatidyl-ethanolamine PE (18:2 (9Z, 12Z)/P-18:0) relative amount substitute into tyrosine, glutamine-leucine and
The binary that phosphatidyl-ethanolamine PE (18:2 (9Z, 12Z)/P-18:0) joint distinguishes health volunteer VS metabolic syndrome patient is patrolled
Regression equation is collected, the regressand value logit [p] of each sample is calculated, with above-mentioned tyrosine, glutamine-leucine and phosphorus
Acyl ethanol amine PE (18:2 (9Z, 12Z)/P-18:0) joint distinguishes the best cut- of health volunteer VS metabolic syndrome patient
Off value is diagnostic threshold, and logit [p] is predicted as metabolic syndrome patient higher than the diagnostic threshold, lower than the diagnostic threshold
It is predicted as health volunteer, to predict that correct sample number divided by total number of samples (580+577=1157) is tyrosine, paddy ammonia
Amide-leucine and phosphatidyl-ethanolamine PE (18:2 (9Z, 12Z)/P-18:0) joint distinguish health volunteer VS Metabolic syndrome
Levy the accuracy of patient, accuracy 80.5%.
6.4 phenylalanines, glutamine-leucine and phosphatidyl-ethanolamine PE (18:2 (9Z, 12Z)/P-18:0) joint
Distinguish the accuracy of health volunteer VS metabolic syndrome patient
It is concentrated in verifying, phenylalanine, glutamine-in health volunteer and metabolic syndrome patient's serum sample is bright
The relative amount of propylhomoserin and phosphatidyl-ethanolamine PE (18:2 (9Z, 12Z)/P-18:0) substitute into phenylalanine, the bright ammonia of glutamine-
Acid and phosphatidyl-ethanolamine PE (18:2 (9Z, 12Z)/P-18:0) joint distinguish the two of health volunteer VS metabolic syndrome patient
The regressand value logit [p] of each sample is calculated in metalogic regression equation, with above-mentioned phenylalanine, the bright ammonia of glutamine-
Acid and phosphatidyl-ethanolamine PE (18:2 (9Z, 12Z)/P-18:0) joint distinguish health volunteer VS metabolic syndrome patient most
Good cut-off value is diagnostic threshold, and logit [p] is predicted as metabolic syndrome patient higher than the diagnostic threshold, is lower than the diagnosis
Threshold value is predicted as health volunteer, to predict that correct sample number divided by total number of samples (580+577=1157) is phenylpropyl alcohol
Propylhomoserin, glutamine-leucine and phosphatidyl-ethanolamine PE (18:2 (9Z, 12Z)/P-18:0) joint distinguish health volunteer VS
The accuracy of metabolic syndrome patient, accuracy 82.6%.
6.5 7 target metabolite joints distinguish the accuracy of health volunteer VS PATIENTS WITH LARGE BOWEL
It is concentrated in verifying, by the relative amount of seven target metabolites in health volunteer and Serum In Patients With Colorectal Carcinoma sample
The dualistic logistic regression equation that seven target metabolite joints distinguish health volunteer VS PATIENTS WITH LARGE BOWEL is substituted into, is calculated every
The regressand value logit [p] of a sample is diagnosed with above-mentioned seven target metabolites and is distinguished health volunteer VS PATIENTS WITH LARGE BOWEL most
Good cut-off value is diagnostic threshold, and logit [p] is predicted as health volunteer higher than the diagnostic threshold, is lower than the diagnostic threshold
Be predicted as PATIENTS WITH LARGE BOWEL, to predict that correct sample number divided by total number of samples (580+437=1017) is seven targets
Metabolin joint distinguishes the accuracy of health volunteer VS PATIENTS WITH LARGE BOWEL, accuracy 99.3%.
6.6 7 target metabolite joints distinguish the accuracy of metabolic syndrome patient VS PATIENTS WITH LARGE BOWEL
Concentrated in verifying, by metabolic syndrome patient and Serum In Patients With Colorectal Carcinoma sample seven target metabolites it is opposite
Content substitutes into the dualistic logistic regression equation that seven target metabolite joints distinguish metabolic syndrome patient VS PATIENTS WITH LARGE BOWEL, meter
Calculation obtains the regressand value logit [p] of each sample, and it is big to diagnose differentiation metabolic syndrome patient VS with above-mentioned seven target metabolites
The best cut-off value of patients with bowel cancer is diagnostic threshold, and the metabolic syndrome that is predicted as that logit [p] is higher than the diagnostic threshold is suffered from
Person is predicted as PATIENTS WITH LARGE BOWEL lower than the diagnostic threshold, to predict correct sample number divided by total number of samples (577+437=
It 1014) is that seven target metabolites combine the accuracy for distinguishing metabolic syndrome patient VS PATIENTS WITH LARGE BOWEL, accuracy is
99.3%.
6.5 7 target metabolite joints distinguish the accuracy of health volunteer VS metabolic syndrome patient
Concentrated in verifying, by health volunteer and metabolic syndrome patient's serum sample seven target metabolites it is opposite
Content substitutes into the dualistic logistic regression equation that seven target metabolite joints distinguish health volunteer VS metabolic syndrome patient, meter
Calculation obtains the regressand value logit [p] of each sample, and it is comprehensive to diagnose differentiation health volunteer VS metabolism with above-mentioned seven target metabolites
The best cut-off value of simulator sickness patient is diagnostic threshold, and the metabolic syndrome that is predicted as that logit [p] is higher than the diagnostic threshold is suffered from
Person is predicted as health volunteer lower than the diagnostic threshold, to predict correct sample number divided by total number of samples (580+577=
It 1157) is that seven target metabolites combine the accuracy for distinguishing health volunteer VS metabolic syndrome patient, accuracy is
83.8%.
As a result as it can be seen that multiple target metabolites joint distinguishes health volunteer, metabolic syndrome patient or PATIENTS WITH LARGE BOWEL
Accuracy it is higher, there is the diagnostic value for preferably distinguishing health volunteer, metabolic syndrome patient or PATIENTS WITH LARGE BOWEL.
Embodiment 2: the diagnostic kit of health volunteer, metabolic syndrome patient or PATIENTS WITH LARGE BOWEL is distinguished in diagnosis
1, a kind of diagnosis of colorectal carcinoma kit, the early stage for suffering from colorectal cancer for Healthy People or metabolic syndrome patient examine
It is disconnected, wherein the standard items containing diagnosis marker, the diagnosis marker be isoleucine, tyrosine, phenylalanine, tryptophan,
Glutamine-leucine, p-Coumaric Acid or phosphatidyl-ethanolamine PE (18:2 (9Z, 12Z)/P-18:0).
2, a kind of diagnosis of colorectal carcinoma kit, the early stage for suffering from colorectal cancer for Healthy People or metabolic syndrome patient examine
Disconnected, wherein the standard items containing diagnosis marker, which includes tyrosine and glutamine-leucine.
3, a kind of diagnosis of colorectal carcinoma kit, the early stage for suffering from colorectal cancer for Healthy People or metabolic syndrome patient examine
Disconnected, wherein the standard items containing diagnosis marker, which includes isoleucine, tyrosine, phenylalanine, color ammonia
Acid, glutamine-leucine, p-Coumaric Acid and phosphatidyl-ethanolamine PE (18:2 (9Z, 12Z)/P-18:0).
4, a kind of metabolic syndrome diagnostic kit, the early diagnosis of metabolic syndrome is suffered from for Healthy People, wherein containing
There are the standard items of diagnosis marker, which includes tyrosine, glutamine-leucine and phosphatidyl-ethanolamine PE
(18:2(9Z,12Z)/P-18:0)。
5, a kind of metabolic syndrome diagnostic kit, the early diagnosis of metabolic syndrome is suffered from for Healthy People, wherein containing
There are the standard items of diagnosis marker, which includes phenylalanine, glutamine-leucine and phosphatidyl-ethanolamine PE
(18:2(9Z,12Z)/P-18:0)。
6, a kind of metabolic syndrome diagnostic kit, the early diagnosis of metabolic syndrome is suffered from for Healthy People, wherein containing
There are the standard items of diagnosis marker, which includes isoleucine, tyrosine, phenylalanine, tryptophan, glutamy
Amine-leucine, p-Coumaric Acid and phosphatidyl-ethanolamine PE (18:2 (9Z, 12Z)/P-18:0).
The effect of above-described embodiment is specifically to introduce essentiality content of the invention, but those skilled in the art should know
Protection scope of the present invention should not be confined to the specific embodiment by road.
Claims (3)
1. a kind of amino acid, dipeptides or combinations thereof object are suffered from greatly in preparation for early diagnosing Healthy People or metabolic syndrome patient
Application in terms of the diagnostic kit of intestinal cancer;The amino acid be isoleucine, tyrosine, phenylalanine or tryptophan, it is described
Dipeptides is glutamine-leucine.
2. application according to claim 1, it is characterised in that: contain amino acid, dipeptides or combinations thereof in diagnostic kit
The standard items of object;The amino acid is isoleucine, tyrosine, phenylalanine or tryptophan, and dipeptides is the bright ammonia of glutamine-
Acid.
3. application according to claim 2, it is characterised in that: the standard items also containing internal standard compound.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201811289653.0A CN109307774B (en) | 2018-10-31 | 2018-10-31 | A kind of amino acid, dipeptides or combinations thereof application of the object in terms of colorectal cancer early diagnosis |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201811289653.0A CN109307774B (en) | 2018-10-31 | 2018-10-31 | A kind of amino acid, dipeptides or combinations thereof application of the object in terms of colorectal cancer early diagnosis |
Publications (2)
Publication Number | Publication Date |
---|---|
CN109307774A true CN109307774A (en) | 2019-02-05 |
CN109307774B CN109307774B (en) | 2019-12-03 |
Family
ID=65222504
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201811289653.0A Active CN109307774B (en) | 2018-10-31 | 2018-10-31 | A kind of amino acid, dipeptides or combinations thereof application of the object in terms of colorectal cancer early diagnosis |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN109307774B (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113237941A (en) * | 2021-03-31 | 2021-08-10 | 中国人民解放军军事科学院军事医学研究院 | Dipeptide metabolite marker for detecting early intestinal injury by acute ionizing radiation and application thereof |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101960310A (en) * | 2008-03-04 | 2011-01-26 | 味之素株式会社 | Method for evaluating cancer species |
CN107064508A (en) * | 2017-04-21 | 2017-08-18 | 深圳大学 | Aid in colorectal cancer early diagnosis and molecular marker and its application of Prognosis scoveillance |
-
2018
- 2018-10-31 CN CN201811289653.0A patent/CN109307774B/en active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101960310A (en) * | 2008-03-04 | 2011-01-26 | 味之素株式会社 | Method for evaluating cancer species |
CN107064508A (en) * | 2017-04-21 | 2017-08-18 | 深圳大学 | Aid in colorectal cancer early diagnosis and molecular marker and its application of Prognosis scoveillance |
Non-Patent Citations (4)
Title |
---|
BUDHATHOKI,S等: "Association of plasma concentrations of branched-chain amino acids with risk of colorectal adenoma in a large Japanese population", 《ANNALS OF ONCOLOGY》 * |
GAO,P等: "Tissue amino acid profile could be used to differentiate advanced adenoma from colorectal cancer", 《JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS》 * |
沙立娜: "大肠癌患者氨基酸代谢的临床研究", 《中国优秀硕士学位论文全文数据库医药卫生科技辑》 * |
肖亚青等: "基于1H-NMR谱的大肠癌血清代谢组学研究", 《全国肿瘤流行病学和肿瘤病因学学术会议论文集》 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113237941A (en) * | 2021-03-31 | 2021-08-10 | 中国人民解放军军事科学院军事医学研究院 | Dipeptide metabolite marker for detecting early intestinal injury by acute ionizing radiation and application thereof |
Also Published As
Publication number | Publication date |
---|---|
CN109307774B (en) | 2019-12-03 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN109239346B (en) | Application of one group of metabolic markers in terms of metabolic syndrome early diagnosis | |
CN106405104A (en) | Novel liver cirrhosis or liver fibrosis marker | |
Chau et al. | Evaluation of performance of measurement of faecal α1-antitrypsin clearance and Technetium-99m human serum albumin scintigraphy in protein-losing enteropathy | |
CN104634907B (en) | Application of amino acid molecular combination as gastric cancer marker | |
Cox et al. | Measurement of small intestinal permeability markers, lactulose, and mannitol in serum (results in celiac disease) | |
Okamoto et al. | Diagnostic modeling with differences in plasma amino acid profiles between non-cachectic colorectal/breast cancer patients and healthy individuals | |
CN109307774B (en) | A kind of amino acid, dipeptides or combinations thereof application of the object in terms of colorectal cancer early diagnosis | |
CN112230003A (en) | Use of three serum lipids in combination for diagnosis of diabetic nephropathy | |
Sebestyen et al. | The teenager with asymptomatic proteinuria: think orthostatic first | |
Goh et al. | Effect of gluten-free diet on growth and glycemic control in children with type 1 diabetes and asymptomatic celiac disease | |
CN109212216B (en) | The application of p-Coumaric Acid or phosphatidyl-ethanolamine in terms of colorectal cancer early diagnosis | |
CN1068946C (en) | Cancer uroscopy colorimetric method and device | |
CN118011003A (en) | Biomarker composition for diagnosing gastric cancer and application thereof | |
CN101382537A (en) | Gastric cancer diagnosis method | |
CN114965415A (en) | Method for screening cancers through expiration based on metal organic framework structure material | |
CN103278579B (en) | Plasma metabolism micromolecular marker related to human intestinal canal aganglionosis and application of plasma metabolism micromolecular marker | |
Li et al. | Clinical significance of serum cystatin C in early evaluation of renal impairment caused by chemotherapy in elderly patients | |
CN112946303A (en) | Application of TAG54:2-FA18:1 and composition thereof in diagnosis of diabetes and diabetic nephropathy | |
Sakamaki et al. | Small intestinal bacterial overgrowth diagnosed by a breath test and improved by rifaximin in a patient with hepatic encephalopathy and alcoholic liver cirrhosis | |
Tokushima et al. | Intravascular large B-cell lymphoma presenting with hypoxemia without any abnormalities on standard imaging studies | |
Li et al. | Study on the Correlation Between Urinary Transferrin and Nonalcoholic Fatty Liver Disease. | |
CN109061179A (en) | Application of the amino acid combined factor in building colorectal cancer hematology diagnostic model | |
Atay et al. | Evaluation of non-invasive diagnostic methods as indicators of fibrosis in patients with nonalcoholic fatty liver disease | |
Hydzik et al. | Usefulness of 13C-methacetin breath test in liver function testing in Amanita phalloides poisoning; breast feeding woman case | |
CN113447586B (en) | Marker for cardiac cancer screening and detection kit |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |