CN105929180A - Serum marker for lung cancer and application thereof - Google Patents
Serum marker for lung cancer and application thereof Download PDFInfo
- Publication number
- CN105929180A CN105929180A CN201610389698.XA CN201610389698A CN105929180A CN 105929180 A CN105929180 A CN 105929180A CN 201610389698 A CN201610389698 A CN 201610389698A CN 105929180 A CN105929180 A CN 105929180A
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- Prior art keywords
- lung cancer
- serum
- idh2
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- mark
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Classifications
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- 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
- G01N33/6884—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids from lung
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- 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
- G01N33/57423—Specifically defined cancers of lung
-
- 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
- G01N33/57484—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
- G01N33/57488—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites involving compounds identifable in body fluids
Abstract
The invention discloses a serum marker for lung cancer. The serum marker is made of isocitrate dehydrogenase 2, and the content of the isocitrate dehydrogenase 2 in the serum of a patient in the first period of lung cancer can be determined preliminarily. The content of the serum marker in the serum of a patient in the first period of lung cancer after operation is lowered, and the serum marker can be used as a candidate marker for a lung cancer patient after operation.
Description
Technical field
The invention belongs to biomedical sector, be specifically related to a kind of Sera of Lung Cancer mark and application thereof.
Background technology
Tumor marker is that tumor cell produces and certain material of release, often with metabolites such as antigen, enzyme, hormones
In form is present in tumor cell or in host body fluids, according to it is biochemical or immunological characteristic can identify or diagnosing tumour.Swollen
Tumor label is mainly used in the discovery to primary tumo(u)r, the screening of tumor high-risk, benign and malignant tumor clinically
Differential Diagnosis, the judgement of tumor development degree, the O&A of oncotherapy effect and tumor recurrence and prognosis
Prediction etc..Can pass through biochemical reaction, put the method for exempting from, enzyme exempt from the method such as method, electrochemiluminescence detection.
Isocitrate dehydrogenase 2 (isocitrate dehydrogenase 2, IDH2) is participation tricarboxylic acid cycle in cellular metabolic pathways
Enzyme, be positioned at chromosome 15q26.1, Subcellular Localization is in mitochondrial matrix.Its physiological function is that forward is catalyzed 1-Hydroxy-1,2,3-propanetricarboxylic acid.
Oxidation produces α-ketoglutaric acid, and reduction NADP+ produces NADPH simultaneously.The backward reaction catalysis α-ketoglutaric acid of IDH2
Produce 1-Hydroxy-1,2,3-propanetricarboxylic acid., and consume NADPH generation NADP+.
Recent study has reported that IDH2 sudden change produces carcinogenic metabolites 2-hydroxyl 1,3-propanedicarboxylic acid, can suppress glioma differentiation and promote
Enter tumor to be formed.Transplanted tumor in IDH2 knock out mice body is formed and is substantially suppressed, tumor-blood-vessel growth mark
Significantly reduce.Metabolism reprogramming and the angiogenesis of its homologous protein IDH3a induction HIF1 α approach promote tumor growth.
During IDH1/2 backward reaction, consume NADPH, but its product malic acid Transshipment Permitted produces through malate dehydrogenase to endochylema
NADPH, reduces the ROS level of cell, maintains cellular redox state balance, promotes cell survival.IDH2 also may be used
To produce citric acid by glutamine metabolism through a-ketoglutaric acid at hypoxia condition, thus promote cell proliferation and increase thin
Born of the same parents' vigor.
Summary of the invention
The present inventor's inquiry by Big Clinical Samples data base, finds that the high expressed of IDH2 reduces lung cancer patient
Overall survival and Progression free survival phase, prompting IDH2 may participate in generation and the disease progression of pulmonary carcinoma.Use further
Enzyme Linked Immunoadsorbent Assay (ELISA) method to pulmonary carcinoma I phase patient's and healthy population serum I DH2 content carried out point
Analysis, and compare the content of Lung Cancer Cases After Resection Post operation and preoperative patient's serum I DH2.Find that IDH2 is at Serum of Patients with Lung Cancer
In content substantially increase, and Lung Cancer Cases After Resection Post operation the most preoperative serum I DH2 content reduce.Therefore, in serum
IDH2 content may be used for the examination of pulmonary carcinoma and diagnosis, the candidate markers of surgical result.That is, the present invention provides
A kind of Sera of Lung Cancer mark, this mark is IDH2.This mark can be used for preparing the medicine of diagnosing, treatment
The medicine of pulmonary carcinoma, the test kit of diagnosing and pulmonary cancer diagnosis chip.
In a word, IDH2 content in the serum of pulmonary carcinoma I phase patient increases, and whether can suffer from examinee at the beginning of pulmonary carcinoma carries out
Step determines.This tumor markers reduces at pulmonary carcinoma I phase patient Post operation serum content, can control as lung cancer patient operation
The candidate markers treated.
Accompanying drawing explanation
Fig. 1 is embodiment 1 experimental result picture: Fig. 1 a with 1b show IDH2 express the Overall survival of corresponding lung cancer patient with
The Progression free survival phase；
Fig. 2 is embodiment 2 experimental result picture: Fig. 2 a show IDH2 after patients with lung cancer is made a definite diagnosis before operative treatment with healthy population
The protein content of IDH2 in serum, Fig. 2 b shows that adenocarcinoma of lung, lung squamous cancer contain with the albumen of IDH2 in healthy population serum
Amount, Fig. 2 c show before Operation for Lung Cancer excision tumor body with excision after the protein content of IDH2 in serum.
Detailed description of the invention
Embodiment 1.IDH2 is expressed height and is had relatedness with lung cancer patient Overall survival and Progression free survival phase
A large amount of pulmonary carcinoma sample gene expression and clinical information thereof are comprised at present, such as life cycle and Progression free survival phase etc.
Data base, it is provided that disclosed data are for researcher analysis.Total life span for research IDH2 with lung cancer patient is controlled with disease
Treating the relation to first evolution time, applicant transfers IDH2 in clinical sample data base and expresses and total existence of lung cancer patient
Phase and the data of Progression free survival phase, be analyzed statistics.
Experimental technique:
Expressed and data life cycle by IDH2 in inquiry kmplot data base (comprising 1928 example pulmonary carcinoma samples).Use
Cox Functional Analysis data life cycle, draw IDH2 and express and Kaplan-Meier curve life cycle, and carry out statistics and divide
Analysis.
Experimental result:
As shown in Figure 1a, IDH2 high expressed reduces the Overall survival of lung cancer patient, and value-at-risk is 1.27
(95%CI=1.12-1.45), result has significant difference (P=0.00023).As shown in Figure 1 b, IDH2 high expressed
Reducing the Progression free survival phase of lung cancer patient, value-at-risk is 1.37 (95%CI=1.13-1.66), and result has significant difference
(P=0.0014).
Embodiment 2.IDH2 is at patients with lung cancer and healthy population serum, and there were significant differences for the postoperative and preoperative serum of patients with lung cancer.
72 example Healthy Peoples and 28 example pulmonary carcinoma I phase clinical samples peripheral blood serum I DH2 content are examined by this part research
Surveying, wherein 28 example pulmonary carcinoma include 20 example adenocarcinoma and 8 example scale cancer samples.28 example patients with lung cancer all use excision pulmonary carcinoma group
The therapeutic modality knitted, and within before operative treatment and after treatment about 7 days, gather peripheral blood serum, frozen in-80 degree.Healthy People
Group's peripheral blood sample is frozen in-80 degree.
Experimental technique:
USCN company IDH2 Enzyme-linked Immunosorbent Assay (ELISA) detection kit measures IDH2 expression in serum
1. prepare reagent, sample and standard substance；
2. add 100 microliters of sample and standard substance in reacting hole, hatch 2 hours for 37 degree；
3. remove liquid in reacting hole, add 100 microlitre detectable A, hatch 1 hour for 37 degree；
4. removing liquid in reacting hole, rinsing liquid rinses 3 times；
5. add 100 microlitre detectable B, hatch 30 minutes for 37 degree；
6. removing liquid in reacting hole, rinsing liquid rinses 5 times；
7. add 90 il of substrate, hatch 10-20 minute for 37 degree；
8. adding 90 microliter of stop solution, 450nm reads light absorption value immediately.
Experimental result:
Before and after healthy population, Operation for Lung Cancer treatment, serum detects IDH2 protein content to find:
1. lung cancer patient serum I DH2 content relative healths crowd significantly raised (Fig. 2 a).
2. pulmonary carcinoma includes adenocarcinoma and the big main Types of scale cancer two, and IDH2 IDH2 content in adenocarcinoma and scale cancer serum is the brightest
Significant difference is different, all raises (Fig. 2 b) relative to healthy population.
3. pulmonary carcinoma I phase patient is after excision cancerous lung tissue, and serum I DH2 content substantially reduces (Fig. 2 c).
Claims (5)
1. a Sera of Lung Cancer mark, it is characterised in that described mark is Isocitrate dehydrogenase 2.
2. mark application in preparing diagnosing medicine as claimed in claim 1.
3. the mark as claimed in claim 1 application in preparation treatment lung-cancer medicament.
4. mark application in preparing diagnosing test kit as claimed in claim 1.
5. mark application in preparing pulmonary cancer diagnosis chip as claimed in claim 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610389698.XA CN105929180B (en) | 2016-06-02 | 2016-06-02 | A kind of Sera of Lung Cancer mark and its application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610389698.XA CN105929180B (en) | 2016-06-02 | 2016-06-02 | A kind of Sera of Lung Cancer mark and its application |
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| Publication Number | Publication Date |
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| CN105929180A true CN105929180A (en) | 2016-09-07 |
| CN105929180B CN105929180B (en) | 2017-10-20 |
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| CN201610389698.XA Active CN105929180B (en) | 2016-06-02 | 2016-06-02 | A kind of Sera of Lung Cancer mark and its application |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103163293A (en) * | 2012-06-19 | 2013-06-19 | 中国医学科学院肿瘤医院 | Test kit of auxiliary diagnosis of non-small cell lung cancer patients |
| WO2014163849A1 (en) * | 2013-03-12 | 2014-10-09 | Novartis Ag | Markers for isocitrate dehydrogenase inhibitors |
-
2016
- 2016-06-02 CN CN201610389698.XA patent/CN105929180B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103163293A (en) * | 2012-06-19 | 2013-06-19 | 中国医学科学院肿瘤医院 | Test kit of auxiliary diagnosis of non-small cell lung cancer patients |
| WO2014163849A1 (en) * | 2013-03-12 | 2014-10-09 | Novartis Ag | Markers for isocitrate dehydrogenase inhibitors |
Non-Patent Citations (2)
| Title |
|---|
| 李昆等: "高湿环境对大鼠肝脏异柠檬酸脱氢酶及α-酮戊二酸脱氢酶的影响", 《第三军医大学学报》 * |
| 陆建红等: "干扰IDH-2 基因对小细胞肺癌生长抑制作用的研究", 《中国病理生理杂志》 * |
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| Publication number | Publication date |
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| CN105929180B (en) | 2017-10-20 |
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Effective date of registration: 20221110 Address after: 411103 Academician Building of the Third Medical Innovation Center, No. 5, Qinglan Road, Zhaoshan Town, Yuetang District, Xiangtan City, Hunan Province Patentee after: Hunan Xintu Medical Diagnostic Technology Co.,Ltd. Address before: Yuelu District City, Hunan province 410083 Changsha Lushan Road No. 932 Patentee before: CENTRAL SOUTH University |
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