Leveraging Bioinformatics and Machine Learning for Identifying Prognostic Biomarkers and Predicting Clinical Outcomes in Lung Adenocarcinoma.

Journal: Genes
PMID:

Abstract

There exist significant challenges for lung adenocarcinoma (LUAD) due to its poor prognosis and limited treatment options, particularly in the advanced stages. It is crucial to identify genetic biomarkers for improving outcome predictions and guiding personalized therapies. In this study, we utilize a multi-step approach that combines principled sure independence screening, penalized regression methods and information gain to identify the key genetic features of the ultra-high dimensional RNA-sequencing data from LUAD patients. We then evaluate three methods of survival analysis: the Cox model, survival tree, and random survival forests (RSFs), to compare their predictive performance. Additionally, a protein-protein interaction network is used to explore the biological significance of identified genes. and are consistently selected as significant predictors across all feature selection methods. The Kaplan-Meier method shows that high expression levels of these genes are strongly correlated with poorer survival outcomes, suggesting their potential as prognostic biomarkers. RSF outperforms Cox and survival tree methods, showing higher AUC and C-index values. The protein-protein interaction network highlights key nodes such as and , which play central roles in LUAD progression. Our findings provide valuable insights into the genetic mechanisms of LUAD. These results contribute to the development of more accurate prognostic tools and personalized treatment strategies for LUAD.

Authors

  • Kaida Cai
    Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China.
  • Wenzhi Fu
    Department of Statistics and Actuarial Science, School of Mathematics, Southeast University, Nanjing 211189, China.
  • Hanwen Liu
    Physics & Astronomy, University of British Columbia, Canada; International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Canada.
  • Xiaofang Yang
    Department of Cardiac Surgery, The First Hospital of Lanzhou University, Lanzhou, Gansu, China.
  • Zhengyan Wang
    Department of Statistics and Actuarial Science, School of Mathematics, Southeast University, Nanjing 211189, China.
  • Xin Zhao
    Florida International University.