Diagnostic and prognostic biomarkers associated with histotype in advanced epithelial ovarian cancer

Despite advances in cancer treatments, epithelial ovarian cancer (EOC) remains the leading cause of death among gynecologic cancers. EOC is stratified into five main histopathological subtypes: high-grade serous carcinoma (HGSC), low-grade serous carcinoma (LGSC), endometrioid carcinoma (EC), clear cell carcinoma (CCC), and mucinous carcinoma (MC). However, personalized treatment strategies and reliable biomarkers for all histotypes remain elusive. Building on our previous work with early-stage EOC, we aim to explore diagnostic and prognostic biomarkers in advanced-stage EOC, updated to the latest World Health Organization classification guidelines from 2020, using comprehensive transcriptomic profiling from total RNA sequencing of 146 EOCs. Differential expression analysis identified top 9 histotype-specific gene panels for HGSC, CCC, MC, and EC, including S100A1 (HGSC), ARID3A (CCC), LGALS4 (MC), and PAX9 (EC). We also identified gene candidates associated with overall survival and disease-specific survival, reflecting both favorable (e.g., OTOF, EEF1E1-BLOC1S5, and STAC3) and unfavorable (e.g., SMOC1, GDPGP1, EPRS1) clinical outcome. Additionally, enrichment analysis revealed tumor progression-related pathways unique to each histotype, offering insights into the molecular mechanisms underlying disease progression and potential therapeutic targets. These findings provide valuable insights into the molecular landscape of advanced-stage EOC, paving the way for more effective diagnostic and prognostic tools across diverse histotypes.