Co-expression network analysis revealsSMG۸, and PPP۱R۸ as potential biomarkers in incidenceof recurrent GBM

Background: Glioblastoma multiforme (GBM) is adults' mostaggressive and common form of brain cancer. GBM is characterizedby poor survival, remarkably high tumor heterogeneity,and a lack of effective therapies. The median survival of GBMpatients is only ۱۵ months after initial diagnosis and even less aftertumor recurrence. In the present study, we investigated somebiomarkers using systems biology approaches that can affect theincidence of recurrent GBM to prevent disease recurrence.Materials and Methods: Microarray data, including ۵۶ polyclonaland monoclonal glioma stem cell lines from initial diagnosis,were obtained from the GEO database (GSE۱۰۱۱۱۳).TAC software was used to observe gene expression profiling,evaluate data quality and extract differentially expressed genes(DEG) between primary and recurrent GBM. The weighted geneco-expression network analysis (WGCNA) package (۱.۷۱) wasused to construct the co-expression network. Then two moduleswere selected and visualized with Cytoscape software (۳.۹.۱).Furthermore, Gene Ontology and pathway enrichment analyseswere performed using EnrichR database. Survival analysis wasalso conducted to validate target genes.Results: ۱۲۸۵ genes were significantly differentially expressedin recurrent samples compared to primary samples. Among theidentified modules, Lightpink۲ and palevioletred۲ modules containTP۵۳ and COX۱۱ genes, respectively. Ten hub genes, includingSMG۸, AP۴E۱, COX۱۱, VPS۱۸, PPP۱R۸, TP۵۳, OAZ۲,LINC۰۰۴۷۱, MAP۲K۱, LOC۱۰۵۳۷۹۸۷۸ were significantly upregulatedin recurrent vs primary cell lines. These potential markershave a role in Pancreatic cancer, Pancreatic adenocarcinomapathway WP۴۲۶۳, AP-۲ adaptor complex, and histone acetyltransferasebinding. The survival analysis also indicates that the overexpressionof SMG۸, COX۱۱, MAP۲K۱, and PPP۱R۸ significantlycorrelates to lower overall survival in recurrent GBM patients.Conclusion: Our analysis demonstrates some potential targetsthat may contribute to the recurrence of GBM progression andlower overall survival. Further experimental validation is essentialfor confirmation of this role.

کلیدواژه ها:

Glioblastoma multiforme ، Co-expression network ، WGCNA ، recurrent GBM ، TAC software