Integrative multiomic and immune profiling of lung adenocarcinoma: molecular landscapes, gene expression, and treatment response insights

• Published in: The oncologist (Dayton, Ohio) Vol. 30; no. 10
• Main Authors: Dong, Honghong, Tian, Yahui, Guo, Yujie, Xin, Shaowei, Jiang, Suxin, Wan, Zitong, Wang, Huaiyu, Han, Yong
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01.10.2025
• Subjects: Adenocarcinoma of Lung - genetics; Adenocarcinoma of Lung - immunology; Adenocarcinoma of Lung - pathology; Biomarkers, Tumor - genetics; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms - genetics; Lung Neoplasms - immunology; Lung Neoplasms - pathology; Male; Prognosis; Transcriptome; Tumor Microenvironment - immunology; immune profiling; molecular subtypes; differential gene expression; multiomics; lung adenocarcinoma; personalized medicine
• ISSN: 1083-7159; 1549-490X; 1549-490X
• DOI: 10.1093/oncolo/oyaf191

Abstract Background Lung adenocarcinoma (LUAD) is a major cause of cancer death. Traditional histopathological classification overlooks molecular heterogeneity, limiting personalized treatment. This study used multiomic data to define LUAD subtypes, assess prognostic significance, and analyze immune features, aiming to improve targeted therapy and clinical outcomes. Methods This study used Consensus Clustering and Gap Statistics to analyze LUAD multiomic data, including mRNA, lncRNA, miRNA, DNA methylation, and mutations. Clustering was validated by silhouette plots and heatmaps. Molecular characterization involved regulon activity, immune and metabolic profiling. Functional assays (qPCR, WB, CCK-8, flow cytometry) assessed neuronal differentiation factor (NDNF)’s role in LUAD. Results Two molecular LUAD subtypes showed distinct clustering and survival outcomes. One subtype had worse prognosis and unique immune features, including checkpoint expression and microenvironment differences. Gene signatures and metabolism varied by subtype. Neuronal differentiation factor was downregulated in tumors; its overexpression suppressed LUAD cell viability and promoted apoptosis, suggesting tumor-suppressive function. Conclusions This study identifies 2 LUAD subtypes with distinct molecular and immune features linked to prognosis and therapy response. Neuronal differentiation factor downregulation and its tumor-suppressive effects highlight its therapeutic potential. These findings support improved LUAD stratification and personalized treatment strategies.