A sex-informed transcriptomic prognostic score for gynecologic cancers: Multiplatform validation and spatial...

Area of Science:

• Genomics and Computational Biology
• Cancer Research
• Precision Medicine

Background:

• Transcriptomic signatures are crucial for cancer prognosis.
• Sex-specific differences in cancer biology necessitate sex-informed approaches.
• Existing prognostic scores may not fully capture tumor heterogeneity.

Purpose of the Study:

• To develop and validate a sex-informed transcriptomic prognostic score for gynecologic malignancies.
• To assess the score's performance across multiple cohorts and platforms.
• To investigate the biological underpinnings of high-risk scores in gynecologic tumors.

Main Methods:

• Retrospective analysis of transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and CPTAC-3.
• Construction of a 10-gene score using sex-stratified Cox models and LASSO regression.
• Validation across multiple independent cohorts and through spatial transcriptomic analysis.

Main Results:

• The 10-gene score demonstrated strong prognostic discrimination (HR=2.15) with AUCs of 0.69-0.72.
• The score was robust across diverse datasets and analytical platforms.
• In gynecologic tumors, high-score regions correlated with fibroblast-rich, immune-depleted areas, indicating stromal remodeling and immune exclusion.

Conclusions:

• A sex-informed, spatially validated transcriptomic score offers reproducible risk stratification for gynecologic cancers.
• The score captures aggressive tumor states associated with immune evasion.
• This score may enhance biomarker-guided clinical trials and precision oncology implementation.