Integrated Transcriptomic Analysis Identifies Potential Biomarkers in Castration-Resistant Prostate Cancer

Area of Science:

• Molecular Oncology
• Transcriptomics
• Cancer Genomics

Background:

• Castration-resistant prostate cancer (CRPC) is an aggressive form of prostate cancer developing after androgen deprivation therapy.
• While androgen receptor (AR) signaling drives progression, other molecular mechanisms contribute to therapeutic resistance.
• Identifying CRPC's transcriptional programs is crucial for novel biomarker and therapeutic target discovery.

Purpose of the Study:

• To compare transcriptomic profiles of non-malignant prostate epithelial cells with CRPC cells.
• To identify key genes and pathways involved in CRPC progression.
• To validate candidate gene expression in clinical prostate adenocarcinoma samples.

Main Methods:

• RNA sequencing for transcriptomic profiling of PNT2 (non-malignant) and 22Rv1 (CRPC) models.
• Differential gene expression analysis (DESeq2), Gene Ontology (GO), and KEGG pathway analyses.
• Gene co-expression network analysis and clinical validation using GEPIA2 (TCGA and GTEx data).

Main Results:

• Extensive transcriptional remodeling observed in CRPC, with significant dysregulation of genes including MALAT1, FASN, PARP1, SET, ENSG00000214719, and IGF1.
• Enrichment analyses revealed activated metabolic processes, ribosome pathways, nucleic acid binding, and PI3K-Akt signaling.
• An AR-centered network module identified key regulators (PARP1, KDM6B, BAZ2A, RANGAP1, NFAT5, MAP4); FASN, PARP1, SET, and ENSG00000214719 validated in tumors.

Conclusions:

• Integrated transcriptomic and network analyses highlight coordinated metabolic, epigenetic, and DNA damage response pathways in CRPC.
• These findings suggest potential combinatorial therapeutic vulnerabilities in advanced prostate cancer.
• The study identifies key molecular drivers and potential therapeutic targets for CRPC.