AI Article Synopsis
- - The study explored how genetic variations in specific histone modification regions relate to the outcomes of lung adenocarcinoma patients after surgery, focusing on overall and disease-free survival rates.
- - Researchers identified and analyzed 279 significant single nucleotide polymorphisms (SNPs), discovering that the SNP CAPN1 rs17583C>T correlated with improved patient survival, while LINC00959 rs4751162A>G was linked to worse disease-free survival.
- - Additional experiments showed that these SNPs affect gene expression levels, indicating their roles in cancer prognosis and supporting the idea that genetic factors in histone modification may influence lung adenocarcinoma outcomes post-surgery.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8563968 | PMC |
| http://dx.doi.org/10.1038/s41598-021-00909-z | DOI Listing |
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