免疫激活通路中 VAV2 和 PSMA4 的潜在功能遗传变异与非小细胞肺癌的生存。
Potentially functional genetic variants of VAV2 and PSMA4 in the immune-activation pathway and non-small cell lung cancer survival.
机构信息
School of Public Health|Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, China.
Yiwu Research Institute of Fudan University, Yiwu, Zhejiang, China.
出版信息
J Gene Med. 2022 Oct;24(10):e3447. doi: 10.1002/jgm.3447. Epub 2022 Sep 13.
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 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.
背景
肺癌是癌症中死亡率最高的一种，其 5 年生存率较低。免疫系统的功能对肺癌的发生和发展有深远的影响。因此，免疫相关基因的遗传变异可能是预测非小细胞肺癌（NSCLC）患者生存的潜在指标。
方法
本研究在 1531 名 NSCLC 患者中进行了两阶段生存分析，并评估了免疫激活基因座中遗传变异与 NSCLC 患者总生存期（OS）的相关性。对经过多轮测试校正后确定的有效变异进行了功能注释和体外实验。
结果
我们在所有数据集中鉴定出 25 个与 NSCLC OS 相关的 SNP，跨越六个基因座，其中两个变体 PSMA4 rs12901682 A > C 和 VAV2 rs12002767 C > T，通过顺式调控相应基因的表达，可能影响肺癌 OS（HR（95%CI）= 0.76（0.65-0.89）和 1.36（1.12-1.65），p = 4.29 × 10 和 0.002）。
结论
我们的研究结果为免疫激活通路基因遗传变异在肺癌进展中的作用提供了新的见解。
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