2024 Asia Conference on Lung Cancer (ACLC) - Poster & ePosters-PP02.48

PP02.48 - Li Su

Pdf Summary

This study investigates the complex interactions between smoking, DNA methylation, and genes impacting the overall survival (OS) of patients with early-stage non-small-cell lung cancer (NSCLC). Recognizing the role of DNA methylation in tumor progression, the study explores four-way interactions involving smoking and three CpG probes (cg05293407TRIM27, cg00060500KIAA0226, and cg16658473SHISA9) that might affect survival outcomes.<br /><br />Utilizing data from different international cohorts, the research employs a two-phase study design: a discovery phase with data from the USA, Spain, Norway, and Sweden, and a validation phase using data from The Cancer Genome Atlas (TCGA). The study aims to identify gene-smoking interactions that could serve as prognostic indicators. By employing histology-stratified multivariate Cox regression models, the hazard ratios for different genetic interactions were calculated, particularly focusing on those that passed a statistically significant threshold (FDR-q < 0.05).<br /><br />A key takeaway is the development of a TRIUNE risk score, summarizing the four-way interaction's components, and categorizing patients into risk quartiles. Higher TRIUNE scores correlate with shorter survival and increased mortality risk. This score outperforms traditional clinical scores in stratifying patient risk, indicating its potential as a valuable tool in clinical settings.<br /><br />The study finds significant interactions at the gene expression level, indicating pathways related to immune response may contribute to poorer prognosis in NSCLC. However, the study acknowledges the limitation of not elucidating the underlying biological mechanisms of these interactions. Despite this, it successfully highlights the profound impact DNA methylation and smoking have on NSCLC outcomes and provides a framework for further research on prognostic biomarkers.

Keywords

NSCLC

DNA methylation

smoking

survival outcomes

TRIUNE risk score

gene-smoking interactions

prognostic indicators

CpG probes

Cox regression models

immune response