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Molecular marker relevant to non-small-cell lung cancer prognosis and application thereof

A non-small cell lung cancer, molecular marker technology, applied in the determination/examination of microorganisms, biochemical equipment and methods, DNA/RNA fragments, etc. question

Active Publication Date: 2019-05-10
BEIJING INST OF GENOMICS CHINESE ACAD OF SCI CHINA NAT CENT FOR BIOINFORMATION
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Non-small cell lung cancer mainly includes squamous cell carcinoma and adenocarcinoma in terms of histological morphology, which is characterized by a slow onset process and undetectable metastatic spread.
[0003] Non-small cell lung cancer patients are prone to recurrence and metastasis, so the cure rate is extremely low, and the five-year survival rate of patients after surgery is less than 15%
However, as a heterogeneous disease, lung cancer has obvious individual differences. Even individuals with the same pathological classification will still have different drug responses, different treatment effects, and different recurrence times. The prognosis is complicated and difficult to judge.

Method used

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  • Molecular marker relevant to non-small-cell lung cancer prognosis and application thereof
  • Molecular marker relevant to non-small-cell lung cancer prognosis and application thereof
  • Molecular marker relevant to non-small-cell lung cancer prognosis and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0081] Example 1 Lung cancer exosomes transform fibroblasts and affect the protein level secreted to the extracellular space

[0082] Extraction of exosomes secreted by non-small cell lung cancer: Collect the serum-free medium supernatant of cultured lung cancer cell lines. Centrifuge at 3000g for 15 minutes at 4°C, and take the supernatant and place it in a new centrifuge tube. Centrifuge at 16,000g for 1 hour at 4°C, take the supernatant and place it in a new centrifuge tube. Centrifuge at 120,000g for 2 hours at 4°C and discard the supernatant. Resuspend the pellet, ie exosomes, in PBS. Electron microscope identification of the collected exosome structure: take 10ul of the resuspension, drop it on the carbon-containing copper grid, add 2% uranyl acetate after drying, let it stand for 5 minutes, rinse with PBS for 2 minutes, absorb the excess liquid with filter paper, and repeat Wash three times and let dry. Under the 80kV voltage transmission electron microscope, the ex...

Embodiment 2

[0086] Example 2 Establishing a Prognostic Model for Non-small Cell Lung Cancer

[0087] In order to establish a reliable non-small cell lung cancer prognosis model, the present invention collects data sets related to non-small cell lung cancer with survival information. The specific sample information of the dataset is shown in Table 1 and Table 2.

[0088] Table 1. Information of patients with non-small cell lung cancer related to overall survival

[0089]

[0090]

[0091] Table 2. Information of patients with non-small cell lung cancer related to recurrence-free survival

[0092]

[0093]

[0094] The experimental platform of the data set is Affymetrix U133Plus2.0 chip. The gene expression value of each data set is normalized by Z value, that is, (gene expression value - the average value of the gene expression value in the data set) / (the standard deviation of the gene expression value in the data set) ("-" represents minus sign, " / " represents the division ...

Embodiment 3

[0115] Example 3 Application of non-small cell lung cancer prognosis model

[0116] The non-small cell lung cancer prognosis model obtained in the training set obtained in Example 2 is applied to a verification set, three independent test sets related to overall survival and four independent test sets related to recurrence-free survival. Patient survival risk and disease recurrence risk prediction.

[0117]Take the non-small cell lung cancer prognosis model composed of the above five probes to predict the survival rate of the data set related to the overall survival rate as an example. According to the prognosis model, the risk score of each patient in the relevant data set is obtained, and the risk score of the patient is greater than the Patients with a risk score cutoff value corresponding to the prognostic model are classified as high-risk patients, and patients whose risk score is less than the risk score cutoff value corresponding to the gene combination model are classi...

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Abstract

The invention provides a molecular marker relevant to non-small-cell lung cancer prognosis and application thereof. In combination with a non-small-cell lung caner gene chip expression data set, by means of a random forest law and Cox single-factor regression analysis, genes with expression levels remarkably relevant to the lifetime of patients are found in candidate genes, the genes are subjectedto survival analysis modeling through Cox multi-factor regression analysis, the expression of a model is evaluated through a Kaplan Meier method and a time-dependent ROC analysis method, a lung cancer prognosis marker set of 17 genes is obtained, the postoperative patients are subjected to lifetime length and recurrent risk degree classifying through specific gene combinations in the 17 genes respectively, and then individualized treatment is carried out. The molecular marker is not affected by the factors such as the NSCLC organization type, the disease stages, the ages and the genders, canbe used as an NSCLC prognosis evaluation tool, and has common adaptability for the NSCLC patients.

Description

technical field [0001] The invention relates to the field of medical molecular biology, in particular to the technical field of postoperative recurrence evaluation and drug guidance for lung cancer patients, and specifically relates to molecular markers related to the prognosis of non-small cell lung cancer and applications thereof. Background technique [0002] Lung cancer is one of the most common malignant tumors. Lung cancer includes small cell lung cancer and non-small cell lung cancer, among which non-small cell lung cancer accounts for 85% of the overall incidence of lung cancer. Non-small cell lung cancer mainly includes squamous cell carcinoma and adenocarcinoma in histological form, which is characterized by a slow onset process and undetectable metastases. [0003] Patients with non-small cell lung cancer are prone to recurrence and metastasis, so the cure rate is extremely low, and the five-year survival rate of patients after surgery is less than 15%. Although...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6886C12N15/11
Inventor 米双利张健
Owner BEIJING INST OF GENOMICS CHINESE ACAD OF SCI CHINA NAT CENT FOR BIOINFORMATION
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