Journal
JOURNAL OF GENE MEDICINE
Volume 24, Issue 10, Pages -Publisher
WILEY
DOI: 10.1002/jgm.3447
Keywords
functional single nucleotide polymorphism; overall survival; pathway analysis; predictive value
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Funding
- National Natural Science Foundation of China [81902876]
- Shanghai Municipal Health Commission [GWV-10.1-XK16, GWV-10.2-YQ42]
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This study identified genetic variants in the immune-activation gene set that are associated with overall survival in non-small cell lung cancer patients. Two validated variants were found to potentially affect lung cancer survival by regulating the expression of corresponding genes.
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 x 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.
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