Potentially functional genetic variants of VAV2 and PSMA4 in the immune-activation pathway and non-small cell lung cancer survival.
BACKGROUND: Lung cancer has the highest mortality among cancers, represented by a low 5-year survival rate. The function of the immune system has a profound influence on the development and progression of lung cancer. Thus genetic variants of the immune-related genes may serve as potential predictors of non-small cell lung cancer (NSCLC) survival. METHODS: In the present study, we conducted a two-stage survival analysis in 1,531 NSCLC patients and assessed the associations between genetic variants in the immune-activation gene set and the overall survival (OS) of NSCLC patients. The validated variants were further subjected to functional annotation and in vitro experiments. RESULTS: We identified 25 SNPs spanning six loci associated with NSCLC OS after multiple-testing corrections in all datasets, in which two variants, PSMA4 rs12901682 A > C and VAV2 rs12002767 C > T, were shown to potentially affect lung cancer OS by cis-regulating the expression of the corresponding genes [(HR (95% CI) = 0.76 (0.65-0.89) and 1.36 (1.12-1.65), p = 4.29 × 10-4 and 0.002, respectively]. CONCLUSION: Our findings provide new insights into the role of genetic variants in the immune-activation pathway genes in lung cancer progression.
Duke Scholars
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- Survival Rate
- Survival Analysis
- Proto-Oncogene Proteins c-vav
- Proteasome Endopeptidase Complex
- Polymorphism, Single Nucleotide
- Lung Neoplasms
- Humans
- Carcinoma, Non-Small-Cell Lung
- Biotechnology
- 3202 Clinical sciences
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Survival Rate
- Survival Analysis
- Proto-Oncogene Proteins c-vav
- Proteasome Endopeptidase Complex
- Polymorphism, Single Nucleotide
- Lung Neoplasms
- Humans
- Carcinoma, Non-Small-Cell Lung
- Biotechnology
- 3202 Clinical sciences