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Updated: Jul 17, 2026

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

Man Shu1, Leilei Huang1, Yu Chen2

  • 1Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, PR China.

Cancer Letters
|March 28, 2024
PubMed
Summary

A new DNA methylation signature, TLA, accurately predicts survival in driver gene-negative lung adenocarcinoma (LUAD). This four-CpG signature offers a valuable tool for precise risk stratification and potential therapeutic targeting in LUAD patients.

Keywords:
DNA methylationDriver geneLung adenocarcinomaPrognosisTherapeutic target

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Area of Science:

  • Oncology
  • Genomics
  • Epigenetics

Background:

  • Driver gene-negative lung adenocarcinoma (LUAD) presents limited treatment options and poor prognosis.
  • Effective biomarkers for risk stratification in this LUAD subgroup are scarce, hindering personalized treatment strategies.

Purpose of the Study:

  • To develop a DNA methylome-based signature for precise risk stratification in driver gene-negative LUAD.
  • To identify novel therapeutic targets for this challenging LUAD subtype.

Main Methods:

  • Utilized Illumina MethylationEPIC Beadchip to identify differentially methylated CpG sites (DMCs).
  • Developed and validated a four-CpG signature (TLA) in internal and external LUAD cohorts.
  • Assessed TLA's prognostic power and its ability to improve existing nomograms.

Main Results:

  • The TLA signature demonstrated significant prognostic value, predicting shorter overall survival (OS) in high-risk LUAD patients across cohorts.
  • TLA effectively stratified patients into distinct low-risk and high-risk groups with significantly different OS.
  • TLA improved 5-year OS prediction compared to TNM staging alone, showing potential as an independent prognostic factor.

Conclusions:

  • The TLA DNA methylation signature provides a robust tool for risk stratification in driver gene-negative LUAD.
  • TLA enhances prognostic accuracy and may guide treatment decisions for LUAD patients.
  • TLA-associated genes (TAC1, LHX9, ALX1) represent potential therapeutic targets for driver gene-negative LUAD.