The aim of this article was to evaluate whether genetic variants in autophagy-related genes affect the overall survival (OS) of non-small cell lung cancer (NSCLC) patients. We analyzed 14 single nucleotide polymorphisms (SNPs) in core autophagy-related genes for OS in 1,001 NSCLC patients. Three promising SNPs in ATG10 were subsequently annotated by the expression quantitative trait loci (eQTL) and methylation quantitative trait loci (meQTL) analyses based on Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) datasets. We observed that the variants of rs10514231, rs1864182 and rs1864183 were associated with poor lung cancer survival (HR = 1.33, 95% CI = 1.07–1.65; HR = 1.43, 95% CI = 1.13–1.81; HR = 1.38, 95% CI = 1.14–1.68, respectively) and positively correlated with ATG10 expression (all p < 0.05) from GTEx and TCGA datasets. The elevated expression of ATG10 may predict shorter survival time in lung cancer patients in TCGA dataset (HR = 2.10, 95% CI = 1.33–3.29). Moreover, the variants of rs10514231 and rs1864182 were associated with the increased methylation levels of cg17942617 (meQTL), which in turn contributed to the elevated ATG10 expression and decreased survival time. Further functional assays revealed that ATG10 facilitated lung cancer cell proliferation and migration. Our findings suggest that eQTL/meQTL variations of ATG10 could influence lung cancer survival through regulating ATG10 expression.What's new?
Three new loci are under scrutiny as possible instigators of lung cancer. Recent work has shown that genes involved in cellular protein recycling, or autophagy, play a role in cancer progression. In this study, the authors tested 14 small nucleotide polymorphisms in autophagy-related genes, looking for an association with NSCLC survival. Three variants in the ATG10 gene correlated with poor survival and with increased ATG10 expression. The authors went on to show that more ATG10 in lung cancer cells meant lower survival rates. Boosting ATG10 expression, they found, helped cancer cells proliferate and migrate, while stifling its expression thwarted the cancer's spread.