Genetic Variants in Histone Modification Regions Are Associated With the Prognosis of Lung Adenocarcinoma

Abstract

We investigated the association between genetic variants in the histone modification regions and the prognosis of lung adenocarcinoma after curative surgery. Potentially functional SNPs were selected using integrated analysis of ChIP-seq and RNA-seq. The SNPs were analyzed in a discovery set (n=166) and a validation set (n=238). The associations of the SNPs with overall survival (OS) and disease-free survival (DFS) were analyzed. A total of 279 SNPs were selected for genotyping. Among these, CAPN1 rs17583C>T was significantly associated with better OS and DFS (P = 0.001 and P = 0.007, respectively), and LINC00959 rs4751162A>G was significantly associated with worse DFS (P = 0.008). Luciferase assays showed a significantly lower promoter activity of CAPN1 in the rs17583 T allele than C allele (P = 0.008), and consistently the CT+TT genotypes had significantly lower CAPN1 expression than CC genotype (P = 0.01) in clinical samples. The rs4751162 G allele had higher promoter activity of GLRX3 than A allele (P = 0.05). The motif analyses and ChIP-qPCR confirmed that the variants are located in the active promoter/enhancer regions where transcription factor binding occurs. This study showed that genetic variants in the histone modification regions could predict the prognosis of lung adenocarcinoma after surgery.

Genetic Variants in Histone Modification Regions Predict Clinical Outcomes of Pemetrexed Chemotherapy in Lung Adenocarcinoma

“…Based on the roles of RPS3 in previous studies, it is postulated that rs549794-in- duced change in the expression level of RPS3 may contribute to the resistance to PEM chemotherapy and consequently the clinical outcomes in lung adenocarcinoma patients. We also evaluated the effect of rs549794A>G on the clinical outcomes of lung adenocarcinoma patients who underwent curative surgery in a recently published study, but found no significant effect [23]. Considering these findings, it can be assumed that RPS3 is involved in molecular mechanisms of resistance to PEM chemotherapy, rather than directly affecting the disease course of lung adenocarcinoma.…”

“…ChIP-sequencing was performed as described previously [23]. ChIP assays were performed using the Pierce Magnetic ChIP kit (Thermo Fisher Scientific, Waltham, MA, USA).…”

Pyroptosis-Related Gene Model Predicts Prognosis and Immune Microenvironment for Non-Small-Cell Lung Cancer

“…Meanwhile, CAPN1 may be a biomarker of tumor or a potential target used to diagnose and treat lung adenocarcinoma [61]. The CAPN1 rs17583C>T was related to a better prognosis, which provided certification of the functional relationship between genetic mutation and the better clinical outcomes [62]. BNIP3, a member of the Bcl-2 protein family with mitochondrial BH3 [63], affects different ways of cell death in hypoxic conditions [64] and also various metabolic pathways [65,66].…”