Analysis and functional validations of multiple cell death patterns for prognosis in prostate cancer

Area of Science:

• Oncology
• Genomics
• Molecular Biology

Background:

• Prostate cancer (PCa) presents diagnostic challenges due to rising incidence and lack of reliable prognostic markers.
• Cell death patterns are increasingly recognized for their prognostic potential in cancer development.

Purpose of the Study:

• To evaluate 15 cell death patterns for prognostic capabilities in PCa.
• To establish and validate a novel Cell Death Index (CDI) signature for PCa prognosis and treatment guidance.

Main Methods:

• Utilized The Cancer Genome Atlas (TCGA) datasets to identify prognostic cell death patterns.
• Developed a CDI signature using necrosis and cuproptosis-related genes.
• Validated the CDI signature in independent PCa cohorts (DKFZ, MSKCC) and conducted in vitro/in vivo studies.

Main Results:

• The CDI signature demonstrated robust predictive performance across multiple validation sets (e.g., 1-year AUC of 0.866 in TCGA).
• Higher CDI scores correlated with advanced PCa stages, Gleason scores, immune infiltration, gene mutations, and drug sensitivity.
• EDA2R and LOXL2 showed distinct roles in PCa progression, linked to necrosis and cuproptosis, respectively.

Conclusions:

• The novel CDI signature serves as an effective indicator for PCa diagnosis and prognostic assessment.
• This signature holds potential for personalized treatment strategies in prostate cancer management.