Molecular and spatial differences in the tumor microenvironment of high-grade serous ovarian cancers with short versus long-term survival

Key Points

• This research aims to identify biological and molecular differences in the tumor microenvironment of high-grade serous ovarian cancer associated with short-term and long-term survival.
• Tumor samples were collected from 15 short-term survivors and 15 long-term survivors with advanced-stage high-grade serous ovarian cancer.
• Bulk tumor sections underwent whole-genome RNA sequencing and machine learning-based image analysis to examine cell phenotypes and morphometric features.
• Computational analysis quantified proportions of various cell types and identified differences in nuclear texture and collagen architecture.
• Short-term survivors had higher fibroblast content (48.6% vs 33.5%, p < 0.05) and lower cancer cell content (48.0% vs 64.3%, p < 0.05) compared to long-term survivors.
• Short-term survivors exhibited upregulation of fibroblast-associated genes and epithelial-mesenchymal transition markers, while long-term survivors showed enrichment in immune signaling pathways.
• Distinct molecular and spatial profiles were found in tumors from short-term and long-term survivors, suggesting clinical relevance.