Transcriptional pattern enriched for synaptic signaling is associated with shorter survival of patients with high-grade serous ovarian cancer

• DOI: 10.7554/elife.101369.3
• Publication Date: 2025-05-13T15:35:42Z
• Authors: Arkajyoti Bhattac...; Thijs S Stutvoet; Mirela Perla; Stefan Loipfinger; Mathilde Jalving; Anna KL Reyners; Paola D Vermeer; Ronny Drapkin; Marco de Bruyn; Elisabeth GE de V...; Steven de Jong; Rudolf SN Fehrmann
• Keywords: Serous ovarian cancer

Bulk transcriptomic analyses of high-grade serous ovarian cancer (HGSOC) so far have not uncovered potential drug targets, possibly because subtle, disease-relevant transcriptional patterns are overshadowed by dominant, non-relevant ones. Our aim was to uncover disease-outcome-related in HGSOC transcriptomes that may reveal novel targets. Using consensus-independent component analysis, we dissected 678 systemic therapy naïve patients—sourced from public repositories—into statistically independent components (TCs). To enhance c-ICA’s robustness, added 447 non-serous histotypes, low-grade serous, and non-cancerous tissues. Cox regression survival tree analysis were performed determine the association between TC activity overall (OS). Finally, determined OS-associated TCs 11 publicly available spatially resolved transcriptomes. We identified 374 TCs, capturing prominent subtle linked specific biological processes. Six age, tumor stage stratified patients with receiving platinum-based chemotherapy into ten distinct OS groups. Three copy-number alterations affecting expression levels genes involved replication, apoptosis, proliferation, immune activity, replication stress. Notably, identifying shortest captured a pattern synaptic signaling, which active regions within all The signaling-related supports emerging role neurons their axons as hallmark-inducing constituents microenvironment. These might offer target for HGSOC.