Comprehensive data mining reveals RTK/RAS signaling pathway as a promoter of prostate cancer lineage plasticity through transcription factors and CNV
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View abstract on PubMed
Summary
This summary is machine-generated.Prostate cancer lineage plasticity drives neuroendocrine prostate cancer (NEPC). The RTK/RAS pathway significantly influences this plasticity, with specific genes regulating the transition and offering new therapeutic targets for NEPC.
Area Of Science
- Oncology
- Molecular Biology
- Genetics
Background
- Prostate cancer lineage plasticity is a critical factor in the development of neuroendocrine prostate cancer (NEPC).
- The RTK/RAS signaling pathway is implicated in various cancers, but its specific role in prostate cancer lineage plasticity is not well understood.
- The regulatory network connecting RTK/RAS signaling and lineage plasticity in prostate cancer requires further investigation.
Purpose Of The Study
- To comprehensively investigate the link between the RTK/RAS signaling pathway and prostate cancer lineage plasticity.
- To explore the intricate regulatory network governing the interplay between RTK/RAS signaling and lineage plasticity.
- To identify potential therapeutic targets for NEPC by understanding these molecular mechanisms.
Main Methods
- Multi-omics data analysis using clustering (coefficient of argument, neighbor joining), Gene Set Enrichment Analysis (GSEA), ssGSEA, Weighted Gene Co-expression Network Analysis (WGCNA), VIPER, and analysis of prostate cancer single-cell RNA sequencing (scRNA-seq) data.
- Identification and validation of overlapping genes within clustering modules using RT-qPCR.
- Construction of transcriptional regulatory networks and analysis of copy number variations.
Main Results
- Six gene modules were identified, with 300 overlapping genes, including three novel prostate cancer genes upregulated in tumors.
- Module 6 positively correlated with prostate cancer cell stemness, multi-lineage states, and the RTK/RAS signaling pathway.
- Nineteen key genes within the RTK/RAS pathway were found to promote prostate cancer lineage plasticity via transcriptional regulation and copy number variations, with TP63 and FOXO1 acting as suppressors and RORC as a promoter.
Conclusions
- The RTK/RAS signaling pathway plays a significant role in driving prostate cancer lineage plasticity towards NEPC.
- Specific genes and regulatory networks within the RTK/RAS pathway are crucial for this transition.
- This study provides novel insights and potential therapeutic targets for treating NEPC.
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