A comprehensive characterization of the transcriptome in enzalutamide resistance prostate cancer

Abstract

Background: Prostate cancer (PCa) contributes to more than 1.2 million newly diagnosed cases and more than 350,000 deaths each year, making it the second most common malignancy and the fifth leading cause of cancer-related deaths in men worldwide. Treatment of PCa is further complicated by drug resistance to enzalutamide. The present study comprehensively details the genomic characteristics of enzalutamideresistant PCa. Methods:The determination of enzalutamide-related genes in GSE163240 and GSE136129 was conducted by differential expression analysis, gene set enrichment analysis (GSEA) suggested that these genes were highly correlated with immune-related pathways. Subsequently, network analysis including module analysis and degree analysis and univariable cox analysis were conducted, which led to the identification of both hub genes [contactin 2 (CNTN2) and frizzled class receptor 2 (FZD2)].Results: GSEA suggested that these genes were highly correlated with immune-related pathways.Subsequently, network analysis, including module analysis and degree analysis, and univariable Cox analysis resulted in the identification of two hub genes, CNTN2 and FZD2, which were further validated using the Gene Expression Omnibus (GEO) and Molecular Signatures Database (MSigDB). GSEA and CIBERSORT indicated that both hub genes were highly correlated with immune-related functions in PCa. Conclusions:In conclusion, this study comprehensively described the transcriptome landscape of enzalutamide-resistant PCa and identified two hub genes, CNTN2 and FZD2, that play an important role in enzalutamide-mediated immune infiltration in PCa.

PAX6 promotes neuroendocrine phenotypes of prostate cancer via enhancing MET/STAT5A-mediated chromatin accessibility

“…2b). The two pathways are reported to be associated with the NE trans-differentiation of PCa cells [36,37] and to influence expression of NE markers, cell communication related genes and tumor microenvironment regulatory genes, contributing to the aggressive feature and poor prognosis [38][39][40][41][42]. In agreement with the results from the above profiling assay, we also confirmed that expression of PAX6, SYP and NSE was upregulated, and that expression of AR and KLK3 was downregulated in LNCaP ENZ cells compared to the parental LNCaP cells (Fig.…”