Identification of a DNA-methylome-based signature for prognosis prediction in driver gene-negative lung adenocarcinoma

作者：Man Shu, Leilei Huang, Yu Chen, Yanxia Wang, Zhongpeng Xie, Shuhua Li, Jianwen Zhou, Lihong Wei, Tongze Fu, Bixia Liu, Honglei Chen, Kejing Tang, Zunfu Ke · 发表于：Cancer Letters · 年份：2024 · DOI：10.1016/j.canlet.2024.216835 · 被引用次数：2 · 研究领域：RNA modifications and cancer、Epigenetics and DNA Methylation、Cancer-related gene regulation

"Driver gene-negative" lung adenocarcinoma (LUAD) was of rare treatment options and a poor prognosis. Presently, for them, few biomarkers are available for stratification analysis to make appropriate treatment strategy. This study aimed to develop a DNA-methylome-based signature to realize the precise risk-stratifying. Here, an Illumina MethylationEPIC Beadchip was applied to obtain differentially methylated CpG sites (DMCs). A four-CpG-based signature, named as TLA, was successfully established, whose prognosis-predicting power was well verified in one internal (n = 78) and other external (n = 110) validation cohorts. Patients with high-risk scores had shorter overall survival (OS) in all cohorts [hazard ratio (HR): 11.79, 5.16 and 2.99, respectively]. Additionally, it can effectively divide patients into low-risk and high-risk groups, with significantly different OS in the diverse subgroups stratified by the standard clinical parameters. As an independent prognostic factor, TLA may assist in improving the nomogram's 5-year OS-predicting ability (AUC 0.756, 95% CI:0.695-0.816), superior to TNM alone (AUC 0.644, 95% CI: 0.590-0.698). Additionally, the relationship of TLA-related genes, TAC1, LHX9, and ALX1, with prognosis and tumour invasion made them serve as potential therapy targets for driver gene-negative LUAD.