摘要：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.
