{"doi":"10.1101/2025.08.26.672372","title":"Multi-modal characterization of transcriptional programs that drive metastatic cascades to solid sites and ascites in ovarian cancer","abstract":"Ovarian high-grade serous carcinoma (HGSC) is characterized by extensive intra-peritoneal dissemination and tumor heterogeneity. In the metastatic cascade, tumors utilize several transcriptional programs to translocate and survive in distant tissues. Here, we analyzed multi-modal, real-world data from 350 tumor samples across 160 patients with HGSC to identify transcriptional programs that drive intra-peritoneal metastasis and heterogeneity. We identified nine transcriptional programs, including those regulating epithelial-mesenchymal transition and immune modulation and cytoskeletal reorganization, which shape distinct metastatic trajectories to solid and ascitic environments and are associated to treatment response. Our results reveal pronounced intra-patient transcriptional heterogeneity, which in some cases surpassed inter-patient heterogeneity, highlighting the importance of multi-site sampling for accurate prognostication and combinatorial treatments in HGSC. Our extensive characterization offers novel insights into intra-peritoneal metastasis with significant prognostic implications, reveals histomorphological biomarkers for patient stratification and paves the way for innovative therapeutic strategies aimed at impairing cancer cell adaptability and limiting metastasis.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":558903,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9359,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1460131,"name":"Essi Kahelin","orcid":null,"position":1,"is_corresponding":false},{"id":1459680,"name":"Giovanni Marchi","orcid":"0000-0001-9513-1123","position":2,"is_corresponding":false},{"id":1459681,"name":"Oskari Lehtonen","orcid":"0000-0001-7006-8877","position":3,"is_corresponding":false},{"id":1460132,"name":"Shams Salloum","orcid":null,"position":4,"is_corresponding":false},{"id":1459682,"name":"Kari Lavikka","orcid":"0000-0002-4163-4945","position":5,"is_corresponding":false},{"id":737020,"name":"Yilin Li","orcid":"0000-0003-3800-3883","position":6,"is_corresponding":false},{"id":28954,"name":"Felix Dietlein","orcid":"0000-0002-6651-7155","position":7,"is_corresponding":false},{"id":1333251,"name":"Alexandra Lahtinen","orcid":"0000-0001-7179-2680","position":8,"is_corresponding":false},{"id":263334,"name":"Jaana Oikkonen","orcid":"0000-0002-1063-2736","position":9,"is_corresponding":false},{"id":883587,"name":"Sakari Hietanen","orcid":"0000-0003-4734-4743","position":10,"is_corresponding":false},{"id":263333,"name":"Johanna Hynninen","orcid":"0000-0002-0854-7225","position":11,"is_corresponding":false},{"id":1459683,"name":"Antti Häkkinen","orcid":"0000-0002-8081-1588","position":12,"is_corresponding":false},{"id":1459684,"name":"Anni Virtanen","orcid":"0000-0002-7467-8434","position":13,"is_corresponding":false},{"id":343955,"name":"Sampsa Hautaniemi","orcid":"0000-0002-7749-2694","position":14,"is_corresponding":false},{"id":343943,"name":"Kaiyang Zhang","orcid":"0000-0002-0470-9581","position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":null,"created_at":"2026-07-19T02:55:30.312295Z","pmid":"40909508","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}