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Peripheral blood mRNA marker for predicting prognosis of patients with lung adenocarcinoma and screening method and application thereof

A screening method and technology for lung adenocarcinoma, applied in the field of medical molecular biology technology and clinical medicine, can solve problems such as tumors, oncogenes, and tumor suppressor gene expression disorders

Active Publication Date: 2018-12-25
BENGBU MEDICAL COLLEGE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Excessive generation and accumulation of ROS and its derivatives can damage the structure and function of intracellular DNA, lipids, proteins, etc., and then cause the expression disorder of oncogenes and tumor suppressor genes, and finally lead to the occurrence of tumors

Method used

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  • Peripheral blood mRNA marker for predicting prognosis of patients with lung adenocarcinoma and screening method and application thereof
  • Peripheral blood mRNA marker for predicting prognosis of patients with lung adenocarcinoma and screening method and application thereof
  • Peripheral blood mRNA marker for predicting prognosis of patients with lung adenocarcinoma and screening method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0055] Screening method for a group of gene markers that can be used to predict the prognosis of patients with lung adenocarcinoma:

[0056] (1) In order to screen the gene markers for predicting the prognosis of patients with lung adenocarcinoma, the gene expression profiles of wild-type (WT) human lung cancer cell lines and Nrf2 knockout (KD) human lung cancer cell lines were first compared and analyzed using the SAM algorithm . Set the analysis conditions of false positive rate 1.5, the results are shown in figure 1 . figure 1 It showed that compared with the wild-type human lung cancer cell line, 2160 genes were up-regulated and 1643 genes were down-regulated in the Nrf2KD cell line.

[0057] (2) Carry out KEGG pathway analysis (Fisher's exact test) on differentially expressed genes, see figure 2 . figure 2 It was shown that the above-mentioned dysregulated Nrf2 target genes were mainly enriched in cancer-related KEGG entries, such as "colorectal cancer", "prostate ...

Embodiment 2

[0061] The identification method of the gene markers described in Example 1 for predicting the prognosis of patients with lung adenocarcinoma:

[0062] In this example, the 66 gene combinations described in Example 1 are defined as "66-gene markers", and the risk score of each patient in the lung adenocarcinoma discovery population database is performed using the "66-gene markers". Among them, "ALDOA, ALYREF, AP1S1, AP2B1, ARNTL2, AVEN, BYSL, C15orf48, C1orf43, CDK5, CENPH, DDX41, DLAT, DPP3, DPY19L1, ERO1L, FOSL1, FOSL2, GARS, GFPT2, GMFB, GNAI3, IPO4, MAPKAP1 , MAX, METTL5, MRPS12, NAMPT, NOP16, PFKP, PLAU, PPIF, PSMB5, ​​PSMC6, PSME3, RALA, RBM28, RRM1, RRM2, SDHC, SEH1L, SYNCRIP, TIMM50, TOMM5, UPP1, VEGFA, and VTI1B" The weight of the gene is "1"; each of "ABI3BP, ACACB, ANAPC16, C17orf103, ECHDC2, FAM117A, HSD17B14, ITPR2, KIAA0232, METTL7A, MPHOSPH8, PTCH1, RBBP6, RBPMS, RPS6KA5, TTC28, USP3, ZBTB4 and ZNF70" Genes have a weight of "-1". In this embodiment, the risk v...

Embodiment 3

[0071] Verification and application of the "66-gene marker" described in Example 2 to predict the prognosis of lung adenocarcinoma in an independent sample set:

[0072] In order to verify the effectiveness of the "66-gene marker" in predicting the prognosis of lung adenocarcinoma, the expression data of the "66-gene marker" in the verification population database was obtained in this embodiment.

[0073] (1) Kaplan-Meier survival curve analysis verified the correlation between the positive "66-gene marker" in the population database and the recurrence-free survival rate of patients with lung adenocarcinoma.

[0074] In this example, Kaplan-Meier survival analysis was performed on the lung adenocarcinoma patients in the verification population databases from Japan, Sweden and Canada respectively. We use formula 1 to calculate the risk value for each patient, the risk value greater than 0 is a positive patient, and the risk value less than or equal to 0 is a negative patient. ...

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Abstract

The invention provides a peripheral blood mRNA marker for predicting prognosis of patients with lung adenocarcinoma and a screening method and application thereof and belongs to the technical fields of medical molecular biology and clinical medicine. The screening method includes the steps of 1), comparatively analyzing gene expression profiles of wild-type human lung cancer cell lines and Nrf2 gene knockout human lung cancer cell lines to obtain Nrf2 target genes; 2), analyzing the relationship between Nrf2 target gene expression and the prognosis survival rate of lung adenocarcinoma by the aid of a discovery group database and screening out the genes with the Nrf2 target gene expression Wald statistics greater than 2 in the discovery group database to obtain the periphery blood MRNA marker for predicting prognosis of the patients with the lung adenocarcinoma. The marker obtained with the screening method is applied to predicting prognosis of the patients with clinical lung adenocarcinoma, good flexibility, stability and specificity are achieved, and spreading use can be realized.

Description

technical field [0001] The invention belongs to the fields of medical molecular biology technology and clinical medicine technology, and specifically relates to a peripheral blood mRNA marker for prognosis prediction of lung adenocarcinoma patients and a screening method thereof. Background technique [0002] Lung adenocarcinoma (lung adenocarcinoma) is a type of lung cancer, which belongs to non-small cell carcinoma. With the acceleration of my country's industrialization process and the increase of extreme weather such as smog, the incidence of lung adenocarcinoma is increasing year by year and tends to be younger. Therefore, the prognosis of lung adenocarcinoma patients has received more and more attention. In recent years, the rapid development of medicine has prolonged the survival period of patients with lung adenocarcinoma, but there are still large differences in prognosis between individuals. Although postoperative chemotherapy is currently recommended for patients...

Claims

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Application Information

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IPC IPC(8): C12Q1/6886C12N15/11
CPCC12Q1/6886C12Q2600/118C12Q2600/158
Inventor 周童许涛吴凤娇张瑶葛青李芮王亭吕静竹钱中清
Owner BENGBU MEDICAL COLLEGE
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