In:
Scientific Reports, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2021-11-02)
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.
Type of Medium:
Online Resource
ISSN:
2045-2322
DOI:
10.1038/s41598-021-00909-z
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2021
detail.hit.zdb_id:
2615211-3