Unveiling diagnostic biomarkers and therapeutic targets in lung adenocarcinoma using bioinformatics and experimental validation.

Journal: Scientific reports
Published Date:

Abstract

Lung adenocarcinoma (LUAD) is a major challenge in oncology due to its complex molecular structure and generally poor prognosis. The aim of this study was to find diagnostic markers and therapeutic targets for LUAD by integrating differential gene expression analysis, weighted gene co-expression network analysis (WGCNA), and machine learning methods. Differentially expressed genes (DEGs) were identified through the analysis of gene expression data from the Gene Expression Omnibus (GEO) database. Ten of the gene co-expression modules constructed by WGCNA were identified, with the red module having the most significant correlation with clinical features. In addition, a machine learning model constructed based on Stepglm[backward] with the random forest algorithm achieved the highest C-index (0.999) and screened eight core genes, among which ST14 was noted for its excellent predictive ability. Single-cell RNA sequencing of the LUAD samples further analyzed the expression patterns of these genes in 29 cellular subtypes, revealing their significant association with immune cell infiltration. Of particular note, the association of ST14 with clinical prognosis, drug responsiveness, and immune infiltration was validated, while enrichment analysis further clarified its role in key biological pathways. Ultimately, the expression of the core genes was validated experimentally. This study provides new insights into the pathogenesis of LUAD, clarifies potential diagnostic markers and therapeutic targets, and provides an important basis for future clinical interventions.

Authors

  • Sixuan Wu
    Department of Oncology, The First Affiliated Hospital, Hengyang Medical School, University of South China, No. 69 Chuanshan Road, Hengyang, 421001, Hunan, China.
  • Yuanbin Tang
    Department of Oncology, The First Affiliated Hospital, Hengyang Medical School, University of South China, No. 69 Chuanshan Road, Hengyang, 421001, Hunan, China.
  • Qihong Pan
    College of Traditional Chinese Medicine, Nanchang Medical College, Nanchang, Jiangxi, China.
  • Yaqin Zheng
    Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, China.
  • Yeru Tan
    Department of Oncology, The First Affiliated Hospital, Hengyang Medical School, University of South China, No. 69 Chuanshan Road, Hengyang, 421001, Hunan, China. tanyeru@163.com.
  • Junfan Pan
    Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, China. pjf1162482056@163.com.
  • Yuehua Li
    From the Institute of Diagnostic and Interventional Radiology (Y.L., M.Y., X.D., J.Z.) and Department of Cardiology (Z.L., C.S.), Shanghai Jiao Tong University Affiliated Sixth People's Hospital, #600, Yishan Rd, Shanghai, China 200233; Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China (Y.W.); and Department of Radiology, Fuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Centre for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (B.L.).