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Identification of the cytoplasmic DNA-Sensing cGAS-STING pathway-mediated gene signatures and molecular subtypes in prostate cancer

  • 0Department of Urology, West China Hospital of Sichuan University, Sichuan Province, Chengdu, China.
Bmc Cancer +

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June 14, 2024

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June 14, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

This study classifies prostate cancer (PCa) into two subtypes based on the cGAS-STING pathway, identifying distinct genetic markers and tumor microenvironment features for high-risk patients. These findings may guide targeted therapies for better PCa treatment outcomes.

Area Of Science

  • Genomics
  • Oncology
  • Immunology

Background

  • Prostate cancer (PCa) is age-relevant, and the cGAS-STING pathway is implicated in aging and cancer.
  • Classifying PCa based on the cGAS-STING pathway can reveal distinct molecular subtypes.
  • Identifying key genes offers a novel perspective for PCa research and personalized therapy.

Purpose Of The Study

  • To classify prostate cancer (PCa) into distinct molecular subtypes.
  • To identify key genes associated with PCa subtypes and prognosis.
  • To explore the role of the cGAS-STING pathway in PCa pathogenesis and therapeutic strategies.

Main Methods

  • Integrated 29 key genes of the cGAS-STING pathway in 430 PCa patients from TCGA.
  • Analyzed differentially expressed genes and biochemical recurrence (BCR)-free survival-related genes.
  • Assessed tumor stemness, heterogeneity, and tumor microenvironment (TME).

Main Results

  • Classified PCa into two subtypes using AURKB, TREX1, and STAT6; subtype 1 showed significantly worse prognosis (HR: 21.19, p < 0.001).
  • Identified top mutation genes and revealed enrichment of E2F targets, base excision repair, cell cycle, and DNA replication in subtype 1.
  • Subtype 1 exhibited higher T cells follicular helper and lower plasma cells in the TME compared to subtype 2.

Conclusions

  • The cGAS-STING pathway mediates distinct molecular subtypes of PCa.
  • Genetic risk scores and identified subtypes can help identify high-risk PCa patients.
  • These findings may inform pharmacologic therapies targeting the cGAS-STING pathway for PCa treatment.

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