CN107589263B - A kind of small molecule marker indicating lung cancer lymphatic metastasis and the application in terms of diagnosis - Google Patents
A kind of small molecule marker indicating lung cancer lymphatic metastasis and the application in terms of diagnosis Download PDFInfo
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Abstract
The invention discloses a kind of small molecule marker for indicating lung cancer lymphatic metastasis and the application in terms of diagnosis, disclose it is a kind of for indicating the composition of lung cancer lymphatic metastasis, including at least phosphatidylinositols (18:3/0:0)；Preferably, the composition includes phosphatidylinositols (18:3/0:0), lysophosphatidyl choline (18:1) and phenylalanine.Phosphatidylinositols (18:3/0:0) is individually 0.803 for the AUC of diagnosing lymphatic metastasis and the non-lymphatic metastasis of lung cancer, has medium accuracy；Serum paraoxonase acyl inositol (18:3/0:0), lysophosphatidyl choline (18:1) and phenylalanine joint are 0.937 for the AUC of diagnosing lymphatic metastasis and the non-lymphatic metastasis of lung cancer, accuracy with higher, the sensitivity and specificity at excellent diagnostics critical value are 0.9 or more.Prove that the accuracy of serum paraoxonase acyl inositol (18:3/0:0), lysophosphatidyl choline (18:1) and phenylalanine joint for diagnosing lymphatic metastasis and the non-lymphatic metastasis of lung cancer is up to 95% in the further verifying that independent sample is concentrated, clinical value with higher.
Description
Technical field
The invention belongs to accurate diagnostic fields, are related to diagnosis marker and diagnostic kit, and in particular to a kind of indication lung
The small molecule marker of cancer lymphatic metastasis and the application in terms of diagnosis.
Background technique
Lung cancer is a kind of common malignant tumour, and morbidity and mortality occupy first of various malignant tumours, and is in hold
Continuous ascendant trend.Advanced lung cancer may occur in which the transfer of each different organs, can cause corresponding symptom, usually bring pole to patient
Big pain, or even threaten life.Wherein, lung cancer lymphatic metastasis is most commonly seen.The invisible pole of lung cancer lymphatic metastasis
By force, golden hour window has been missed in early days without any sign, when making a definite diagnosis by pathological diagnosis.
The goldstandard that lung cancer lymphatic metastasis is made a definite diagnosis is pathological examination, and this method specificity is high, but have it is traumatic, no
It is easy for patients to accept, and there are certain difficulty for materials.Imageological examination is that current lung cancer diagnosing lymph node metastatsis relies primarily on
Means, but it is at high cost, minimal disease is not easy to detect, is not able to satisfy the requirement of lung cancer lymphatic metastasis early diagnosis.
The exception of blood serum tumor markers is easy to detect often earlier than the exception of iconography, and repeatability is strong, and expense is low,
May all have prompt meaning for the exception without clinically relevant patient with sympotoms, any one marker.Therefore, applicant is intended to
Find the marker that can be used for indicating lung cancer lymphatic metastasis.
Summary of the invention
The purpose of the present invention is to provide a kind of small molecule marker for indicating lung cancer lymphatic metastasis and in terms of diagnosis
Application.
Above-mentioned purpose of the present invention technical scheme is that:
Phosphatidylinositols (18:3/0:0), lysophosphatidyl choline (18:1) or phenylalanine are for indicating lung cancer lymph node
The clinical application of transfer.
It is a kind of for indicating the composition of lung cancer lymphatic metastasis, include at least phosphatidylinositols (18:3/0:0).
Preferably, the composition includes phosphatidylinositols (18:3/0:0), lysophosphatidyl choline (18:1) and benzene
Alanine.
It is highly preferred that the composition further includes internal standard L-2- chlorophenylalanine.
Application of any of the above-described composition in terms of the diagnostic kit of preparation indication lung cancer lymphatic metastasis.
Beneficial effects of the present invention:
In ROC curve analysis, area is bigger under ROC curve, and diagnostic value is bigger.When AUC is 0.5, i.e., anticipate without diagnosis
Justice；AUC indicates that accuracy rate of diagnosis is lower at 0.5~0.7；AUC indicates that diagnostic accuracy is medium at 0.7~0.9；AUC
When > 0.9, indicate that diagnosis has higher accuracy.Phosphatidylinositols (18:3/0:0) is individually used for diagnosing lymphatic metastasis
AUC with the non-lymphatic metastasis of lung cancer is 0.803, has medium accuracy；Serum paraoxonase acyl inositol (18:3/0:0), haemolysis
Phosphatidyl choline (18:1) and phenylalanine are combined is for diagnosing lymphatic metastasis and the AUC of the non-lymphatic metastasis of lung cancer
0.937, accuracy with higher, the sensitivity and specificity at excellent diagnostics critical value are 0.9 or more.In independent sample
The further verifying concentrated proves serum paraoxonase acyl inositol (18:3/0:0), lysophosphatidyl choline (18:1) and phenylalanine connection
The accuracy shared in diagnosing lymphatic metastasis and the non-lymphatic metastasis of lung cancer is up to 95%, clinical diagnosis with higher
Value.
Detailed description of the invention
Fig. 1 is serum paraoxonase acyl inositol (18:3/0:0) individually diagnosing lymphatic metastasis and the non-lymphatic metastasis of lung cancer
ROC curve；
Fig. 2 is serum hemolysis phosphatidyl choline (18:1) individually diagnosing lymphatic metastasis and non-lymphatic metastasis of lung cancer
ROC curve；
Fig. 3 is the ROC curve of Serum Phenylalanine independent diagnosing lymphatic metastasis and the non-lymphatic metastasis of lung cancer；
Fig. 4 is serum paraoxonase acyl inositol (18:3/0:0), lysophosphatidyl choline (18:1), phenylalanine Combining diagnosis lung
The ROC curve of cancer lymphatic metastasis and the non-lymphatic metastasis of lung cancer.
Specific embodiment
Essentiality content of the invention is further illustrated below with reference to embodiment.
Embodiment 1: accuracy of the small molecule marker to indication lung cancer lymphatic metastasis
One, material and method
1, research object
The non-lymphatic metastasis group case of lung cancer lymphatic metastasis group, lung cancer be in March, 2015 in December, 2016 in south
The patient of capital drum tower hospital hospitalization, lung cancer lymphatic metastasis group totally 60, wherein male 34, female 26, age 38-72
Year, average age 45 years old；The non-lymphatic metastasis group case of lung cancer totally 100, wherein male 62, female 38, the age 35-70 years old,
Average age 43 years old.All cases are through clinical and definitive pathological diagnosis.The non-lymphatic metastasis group disease of lung cancer lymphatic metastasis group, lung cancer
Example is divided into two groups at random, and one group is training set, and another group is verifying collection, and group result is as follows.
2, instrument and reagent
High Performance Liquid Chromatography/Mass Spectrometry instrument: Agilent 1200 (G6410A), Agilent company of the U.S.；Ultrapure water system:
Milli-Q, Millipor company of the U.S.；Automatic fluid injector: Agilent company of the U.S.；Methanol, acetonitrile, formic acid, isopropyl
Alcohol, Sigma Co., USA are chromatographically pure or mass spectrum rank.
3, sample collection and pretreatment
Acquire selected personnel's empty stomach blood specimen 3ml static 1h solidification layering, centrifugation in the heparin tube containing heparin sodium
(3000rpm10min) takes supernatant to dispense to centrifuge tube, it is stand-by to be stored in -80 DEG C of refrigerators.
The serum sample thaw at RT of cryo-conservation is mixed, 100 μ L serum is taken to be put into centrifuge tube, 300 μ L acetonitriles are added
It rocks and mixes 15s, be stored at room temperature 15min, 10000rpm is centrifuged 10min (4 DEG C), takes 200 μ L of supernatant, blown at room temperature with nitrogen
Instrument drying, residue are redissolved with 50 μ L acetonitrile/water solvents (3:1), and 13000rpm is centrifuged 10min (4 DEG C), take supernatant that 50 μ L are added
It is mixed after the L-2- chlorophenylalanine internal standard that concentration is 0.02mg/mL spare.
The preparation of Quality Control (QC) sample.In order to observe the stability of test method, it is all added one respectively after every 6 serum
A QC sample.QC sample preparation methods are as follows: the serum sample that room temperature shakes up defrosting takes 5 μ L, and methanol and acetonitrile 1:1 mixed liquor is added
L-2- chlorophenylalanine is added as internal standard.Remaining processing is same as above.
4, HPLC-MS analysis condition
Chromatographic condition: chromatographic column selects ZorbaxSB-C18 column (4.6mm × 100mm, 3.5 μm).Column temperature maintains 45 DEG C,
Flowing phase composition is that A is 0.1% aqueous formic acid of volumetric concentration, and B is 0.1% formic acid acetonitrile solution of volumetric concentration；Gradient elution
Condition: 0~3min is 0~30%B phase, and B is phase linear in 2min increases to 60%, 5~10min linear change to 90%B phase, so
100%B phase is linearly increasing in 10~12min afterwards and keeps 3min；Flow velocity 1.0mL/min；10 μ L of single sample introduction.Mass spectrum item
Part: using ESI, under positive ion mode: capillary voltage 4KV, electron energy 3eV, be delayed solution 5min, ion source temperature 115
DEG C, dry 350 DEG C of temperature degree, dry gas stream speed 9L/min, reference charge-mass ratio (m/z) 80-900, quality full scan range 100-
1000, sweep time 0.03s.
5, data processing and statistical analysis
Calculate the mass spectrum of phosphatidylinositols (18:3/0:0) in each sample, lysophosphatidyl choline (18:1) and phenylalanine
The ratio of the mass spectrum total ion current peak area of total ion current peak area and internal standard L-2- chlorophenylalanine, which is each sample
Middle phosphatidylinositols (18:3/0:0), lysophosphatidyl choline (18:1) and phenylalanine relative amount.Using SPSS 16.0
Software is for statistical analysis to data, and normality distribution inspection is analyzed with 1-sampleK-S, compares between the group of each index content
It is examined compared with One-wayANOVALSD method, the comparison of Positive rate uses chi-square criterion, returns selection variables simultaneously with Logistic
Regression equation is established, ROC curve analysis is carried out to new variables and each single index.
Two, experimental result
1, the opposite of each group serum paraoxonase acyl inositol (18:3/0:0), lysophosphatidyl choline (18:1) and phenylalanine contains
Amount compares
Group difference it was found that, 3 kinds of Tumor Marker Levels are significantly higher than lung cancer in lung cancer lymphatic metastasis group serum
Non- lymphatic metastasis group (P < 0.01), phosphatidylinositols (18:3/0:0) raises 6-8 times in lung cancer lymphatic metastasis group sample,
Lysophosphatidyl choline (18:1) raises 1.5-2.5 times, and phenylalanine raises 2-3 times, phosphatidylinositols (18:3/0:0) up-regulation
It is the most significant.
2, the ROC curve of serum paraoxonase acyl inositol (18:3/0:0), lysophosphatidyl choline (18:1) and phenylalanine point
Analysis
Area is bigger under ROC curve, and diagnostic value is bigger.When AUC is 0.5, i.e., without diagnostic significance；AUC 0.5~
When 0.7, indicate that accuracy rate of diagnosis is lower；AUC indicates that diagnostic accuracy is medium at 0.7~0.9；When AUC > 0.9, indicate to examine
It is disconnected to have higher accuracy.With 16.0 software of SPSS by lung cancer lymphatic metastasis group and the non-lymph node of lung cancer in training set
The relative amount of transfer group serum paraoxonase acyl inositol (18:3/0:0), lysophosphatidyl choline (18:1) and phenylalanine is made respectively
ROC curve, as shown in Fig. 1-3 and table 1.
1 serum paraoxonase acyl inositol (18:3/0:0) of table, lysophosphatidyl choline (18:1) and the individual ROC of phenylalanine are bent
Line analysis
As a result
| Detect marker | AUC | Standard error | 95%CI | P |
| Phosphatidylinositols (18:3/0:0) | 0.803 | 0.029 | 0.762~0.845 | 0.03 |
| Lysophosphatidyl choline (18:1) | 0.635 | 0.038 | 0.594~0.676 | 0.00 |
| Phenylalanine | 0.682 | 0.035 | 0.643~0.728 | 0.01 |
From Fig. 1-3 and table 1 as it can be seen that serum paraoxonase acyl inositol (18:3/0:0) is individually for when indicating lung cancer lymphatic metastasis
With medium accuracy, serum hemolysis phosphatidyl choline (18:1) or phenylalanine are individually used to indicate lung cancer lymphatic metastasis
When have lower accuracy.
3, three marker joint indication lung cancer lymphatic metastasis model buildings and ROC curve analysis
In training set, using lung cancer, whether lymphatic metastasis is dependent variable, serum paraoxonase acyl inositol (18:3/0:0), haemolysis
The relative amount of phosphatidyl choline (18:1) and phenylalanine is independent variable, establishes Logistic regression model.Respectively join in model
Several fitting results are shown in Table 2.Therefore the model obtained is represented by Logit=-3.562+2.694 × phosphatidylinositols (18:3/
0:0)+1.319 × lysophosphatidyl choline (18:1)+1.867 × phenylalanine.
The Logistic Regression Model Simulator parameter of 2 three marker joint indication lung cancer lymphatic metastasis of table
| Variable | Coefficient | Standard error | Wald is examined | P value | OR value |
| Phosphatidylinositols (18:3/0:0) | 2.694 | 0.09 | 23.583 | 0.00 | 1.03 |
| Lysophosphatidyl choline (18:1) | 1.319 | 0.05 | 17.955 | 0.00 | 0.98 |
| Phenylalanine | 1.867 | 0.07 | 20.172 | 0.00 | 2.01 |
| Intercept | -3.562 | 0.47 | 32.085 | 0.01 | 0.22 |
The model passes through likelihood ratio test, this regression model has statistical significance (P < 0.01).With ROC curve method pair
Above-mentioned model carries out value of diagnosis, as a result as shown in Figure 4.
As seen from Figure 4, area is 0.937 under the ROC curve, serum paraoxonase acyl inositol (18:3/0:0), hemolytic phosphatidyl
Choline (18:1) and phenylalanine are combined for indicating lung cancer lymphatic metastasis accuracy with higher, excellent diagnostics critical value
(1.474) sensitivity and specificity at are 0.9 or more.
4, the accuracy of three marker combination indication lung cancer lymphatic metastasis of further verifying is concentrated in verifying
Concentrated in verifying, respectively by serum paraoxonase acyl inositol (18:3/0:0) in each sample, lysophosphatidyl choline (18:
1) and the relative amount of phenylalanine substitutes into above-mentioned regression model, obtains the regressand value of each sample, and regressand value is higher than excellent diagnostics
Critical value 1.474 is predicted as lung cancer lymphatic metastasis, is predicted as the non-lymph of lung cancer lower than the excellent diagnostics critical value 1.474
It carries down shifting, accuracy is 95% (76/80).
In summary, phosphatidylinositols (18:3/0:0) is individually for diagnosing lymphatic metastasis and the non-lymph node of lung cancer
The AUC of transfer is 0.803, has medium accuracy；Serum paraoxonase acyl inositol (18:3/0:0), lysophosphatidyl choline (18:
1) and phenylalanine joint for the AUC of diagnosing lymphatic metastasis and the non-lymphatic metastasis of lung cancer is 0.937, is had higher
Accuracy, the sensitivity and specificity at excellent diagnostics critical value are 0.9 or more.It is further tested what independent sample was concentrated
Card proves that serum paraoxonase acyl inositol (18:3/0:0), lysophosphatidyl choline (18:1) and phenylalanine joint are used for diagnosing
The accuracy of lymphatic metastasis and the non-lymphatic metastasis of lung cancer is up to 95%, clinical value with higher.
Embodiment 2: diagnostic kit
It is a kind of for indicating the diagnostic kit of lung cancer lymphatic metastasis in early days, including phosphatidylinositols (18:3/0:0),
Lysophosphatidyl choline (18:1), phenylalanine and L-2- chlorophenylalanine, phosphatidylinositols (18:3/0:0), hemolytic phosphatidyl
Choline (18:1), phenylalanine carry out qualitative positioning, the third ammonia of L-2- chlorobenzene to target compound in test serum as reference substance
Acid is used as internal standard and is added in test serum sample to lysophosphatidyl choline (18:1), phosphatidylinositols (18:3/0:0), benzene
Alanine relative quantification.
The effect of above-described embodiment indicates that essentiality content of the invention, but protection of the invention is not limited with this
Range.Those skilled in the art should understand that can with modification or equivalent replacement of the technical solution of the present invention are made,
Without departing from the essence and protection scope of technical solution of the present invention.
Claims (2)
1. phosphatidylinositols (18:3/0:0), lysophosphatidyl choline (18:1) and phenylalanine, which are combined, is used to prepare indication lung cancer
The purposes of the diagnostic kit of lymphatic metastasis.
2. purposes according to claim 1, it is characterised in that: further include internal standard L-2- chlorophenylalanine.
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102286370A (en) * | 2010-06-15 | 2011-12-21 | 希森美康株式会社 | Method of determining lymph node metastasis in lung cancer, apparatus for determining lymph node metastasis in lung cancer, and control system |
| CN102445543A (en) * | 2010-10-08 | 2012-05-09 | 中国医学科学院肿瘤研究所 | Reagent for auxiliarily diagnosing lung cancer lymph node metastasis |
| CN105021804A (en) * | 2014-04-30 | 2015-11-04 | 湖州市中心医院 | Application of lung cancer metabolism markers to lung cancer diagnosis and treatment |
| CN105486799A (en) * | 2016-01-25 | 2016-04-13 | 中国药科大学 | Metabolism marker for diagnosis of acute coronary syndrome |
| CN105758966A (en) * | 2016-03-24 | 2016-07-13 | 中国药科大学 | Metabolic marker group for diagnosing coronary heart disease |
| CN105758967A (en) * | 2016-03-24 | 2016-07-13 | 中国药科大学 | Marker group for diagnosing and distinguishing coronary arterial atherosclerosis from stable angina pectoris |
-
2017
- 2017-11-02 CN CN201711065571.3A patent/CN107589263B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102286370A (en) * | 2010-06-15 | 2011-12-21 | 希森美康株式会社 | Method of determining lymph node metastasis in lung cancer, apparatus for determining lymph node metastasis in lung cancer, and control system |
| CN102445543A (en) * | 2010-10-08 | 2012-05-09 | 中国医学科学院肿瘤研究所 | Reagent for auxiliarily diagnosing lung cancer lymph node metastasis |
| CN105021804A (en) * | 2014-04-30 | 2015-11-04 | 湖州市中心医院 | Application of lung cancer metabolism markers to lung cancer diagnosis and treatment |
| CN105486799A (en) * | 2016-01-25 | 2016-04-13 | 中国药科大学 | Metabolism marker for diagnosis of acute coronary syndrome |
| CN105758966A (en) * | 2016-03-24 | 2016-07-13 | 中国药科大学 | Metabolic marker group for diagnosing coronary heart disease |
| CN105758967A (en) * | 2016-03-24 | 2016-07-13 | 中国药科大学 | Marker group for diagnosing and distinguishing coronary arterial atherosclerosis from stable angina pectoris |
Non-Patent Citations (6)
| Title |
|---|
| Metabolic Signatures of Lung Cancer in Biofluids: NMR-Based Metabonomics of Blood Plasma;Claudia M. Rocha等;《Journal of Proteome Research》;20110712;第10卷;第4314-4324页 |
| Metabolomics provide new insights on lung cancer staging anddiscrimination from chronic obstructive pulmonary disease;Stanislaw Deja等;《Journal of Pharmaceutical and Biomedical analysis》;20140821;第100卷;第372页，第377页 |
| Serum lipid profile discriminates patients with early lung cancer from healthy controls;Małgorzata Ros-Mazurczyk等;《Lung Cancer》;20170801;第112卷;第69-74页 |
| 不同转移潜能癌症细胞系的脂组学研究;江孔梅;《中国优秀硕士学位论文全文数据库》;20170815(第2017/08期);全文 |
| 基于LC-MS/MS技术的肺癌血浆代谢组学研究;杨雄;《中国博士学位论文全文数据库》;20131115(第2013/11期);全文 |
| 组合式离子化RRLC-MS/MS方法与~1H NMR技术的肺癌血浆代谢组学分析方法研究;田鹤;《中国博士学位论文全文数据库》;20131115(第2013/11期);全文 |
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