Identification of Potential BRAF Inhibitor Joint Therapy Targets in PTC based on WGCAN and DCGA

In this study, we combined transcript data and clinical information from 199 BRAF wild-type (BRAFWT) patients and 283 BRAFV600E mutant patients collected from The Cancer Genome Atlas (TCGA), and screened 455 BRAFV600E- associated genes through differential analysis and weighted gene co-expression network analysis. Based on these BRAFV600E-associated genes, we performed functional enrichment analysis and co-expression differential analysis and constructed a core co-expression network. Next, genes in the differential co-expression network were used to predict drugs for therapy in the crowd extracted expression of differential signatures (CREEDS) database, and the key genes were selected based on the hub co-expression network through survival analyses and receiver operating characteristic (ROC) curve analyses. Finally, we obtained eight BRAFV600E-associated biomarkers with both prognostic and diagnostic values as potential BRAFi joint targets, including FN1, MET, SLC34A2, NGEF, TBC1D2, PLCD3, PROS1, and NECTIN4. Among these genes, FN1, MET, PROS1, and TBC1D2 were validated through GEO database. Two novel biomarkers, PROS1 and TBC1D2, were further validated by qRT-PCR experiment. Besides, we obtained four potential targeted drugs that could be used in combination with BRAFi to treat PTC, including MET inhibitor, ERBB3 inhibitor, anti-NaPi2b antibody-drug conjugate, and carboplatin through literature review. The study provided potential drug targets for combination therapy with BR...
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Paper Source Type: research