Integrated Bioinformatics Analysis of Human Transcriptomic Data Identifies Three Key Diagnostic and Prognostic...

Lung adenocarcinoma (LUAD) is the leading cause of cancer-related death worldwide. Despite advances in surgery, targeted therapy, and immunotherapy, the 5-year survival rate of advanced LUAD remains below 20%, indicating an urgent need for reliable molecular biomarkers for early detection and prognosis. In this study, the authors hypothesized that three consistently upregulated genes could act as effective diagnostic and prognostic biomarkers for LUAD. The authors analyzed transcriptomic data from two independent cohorts, TCGA-LUAD (535 tumors, 59 normal samples) and GSE115002 (52 tumors, 52 matched normal samples), to screen differentially expressed genes. Three core genes-B3GNT3, FERMT1, and SPP1-were consistently overexpressed in LUAD tumors in both datasets. These genes showed excellent diagnostic performance, with AUC values above 0.95 in TCGA-LUAD and high accuracy in GSE115002. Survival analysis showed that high expression of each gene was significantly associated with shorter overall and disease-free survival, and multivariate Cox regression verified their independent prognostic value. Functional enrichment analysis indicated that these three genes participate in epithelial-mesenchymal transition, extracellular matrix remodeling, and immune suppression, all of which are closely related to LUAD invasion and metastasis. The authors further constructed a prognostic nomogram combining the three genes and TNM stage, achieving a concordance index of 0.743 and demonstrating good predictive performance. These findings confirm that B3GNT3, FERMT1, and SPP1 are promising diagnostic and prognostic biomarkers for LUAD, supporting the clinical application in risk stratification and management.