WGCNA and integrative network analysis identify CHRNA5 and CTLA4 as potential therapeutic targets against angiosarcoma.

Abstract

Angiosarcomas are a type of soft-tissue sarcoma characterized by aggressive malignant tumors originating from endothelial cells of blood vessels or lymphatic vessels. Limited studies have been done to explore the molecular pathophysiology of the disease, with rather limited studies involving transcriptomic analyzes. This study was undertaken to identify the shared molecular signatures and gene modules associated with angiosarcomas of various origin. Transcriptomic data analysis of publicly available data was done followed by WGCNA to identify shared signature gene modules. The Maximal Clique Centrality algorithm was applied to gene modules, and unclustered network analysis was conducted on differentially expressed genes to identify true hub genes. The expression of candidate genes in various cancer types was analyzed using GEPIA. WGCNA analysis identified five significant modules, with the most enriched module being associated with angiogenesis and cell junction regulators. The intersection of true hub genes from MCC analysis of WGCNA modules and high-degree nodes from an unclustered network revealed eight consistently overexpressed genes in all angiosarcoma samples.Among the eight enriched genes, CHRNA5 and CTLA4, are exclusively overexpressed in angiosarcoma and not in other cancers of the same tissue origin, with significant drug-protein interactions suggesting their potential as therapeutic targets.