{"doi":"10.1002/1878-0261.70001","title":"Adverse prognosis gene expression patterns in metastatic castration‐resistant prostate cancer","abstract":"Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease. Several studies have identified transcriptional subtypes of mCRPC, but comprehensive analysis of prognostic gene expression pathways has been limited. Therefore, we aggregated a cohort of 1012 mCRPC tissue samples from 769 patients and investigated the association of gene expression-based pathways with clinical outcomes and intrapatient and intratumor heterogeneity. Survival data were obtained for 272 patients. Pathway-level enrichment was evaluated using gene set variation analysis. scRNA-seq datasets from mCRPC tissue biopsies and circulating tumor cells were used to investigate heterogeneity of adverse pathways. We identified five pathway clusters: (a) Immune response/WNT/TGF-beta signaling, (b) AR signaling/luminal signatures, (c) mTOR signaling and glycolysis, (d) cell proliferation, and (e) neuroendocrine differentiation. Proliferation, AR signaling loss, and glycolysis/mTOR signaling were independently prognostic. Adverse prognostic pathway scores decreased on treatment with AR signaling inhibitors, but not at progression, suggesting failure to permanently target these pathways. scRNA-seq datasets from mCRPC tissue biopsies and circulating tumor cells were used to investigate heterogeneity of adverse pathways. Our results suggest loss of AR signaling, high proliferation, and a glycolytic phenotype as adverse prognostic pathways in mCRPC that could be used in conjunction with clinical factors to prognosticate for treatment decisions.","journal":"Molecular Oncology","year":2025,"id":538024,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9504,"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":893075,"name":"Eric Feng","orcid":"0000-0002-0906-0558","position":1,"is_corresponding":false},{"id":885628,"name":"Nicholas R. 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Blitzer","orcid":"0000-0003-3178-3004","position":11,"is_corresponding":false},{"id":1290395,"name":"Tianfu Andy Shang","orcid":null,"position":12,"is_corresponding":false},{"id":759619,"name":"Aishwarya Subramanian","orcid":"0000-0001-8831-4941","position":13,"is_corresponding":false},{"id":315696,"name":"Anders Bjartell","orcid":"0000-0002-5761-3786","position":14,"is_corresponding":false},{"id":1196288,"name":"Andreas Josefsson","orcid":"0000-0002-2013-0887","position":15,"is_corresponding":false},{"id":1045182,"name":"Pernilla Wikström","orcid":"0000-0002-6347-1999","position":16,"is_corresponding":false},{"id":903804,"name":"Emily Feng","orcid":"0000-0002-1109-4749","position":17,"is_corresponding":false},{"id":263983,"name":"Manish Kohli","orcid":"0000-0002-9735-6614","position":18,"is_corresponding":false},{"id":292243,"name":"Rendong Yang","orcid":"0000-0002-9512-2240","position":19,"is_corresponding":false},{"id":292251,"name":"Scott M. Dehm","orcid":"0000-0002-7827-5579","position":20,"is_corresponding":false},{"id":36082,"name":"Eric J. Small","orcid":"0000-0003-3191-6268","position":21,"is_corresponding":false},{"id":36081,"name":"Rahul Aggarwal","orcid":"0000-0001-7003-7982","position":22,"is_corresponding":false},{"id":292249,"name":"David A. Quigley","orcid":"0000-0002-4726-1473","position":23,"is_corresponding":false},{"id":395994,"name":"Joshua M. Lang","orcid":"0000-0002-0943-8872","position":24,"is_corresponding":false},{"id":238040,"name":"Shuang G. Zhao","orcid":"0000-0002-9166-6507","position":25,"is_corresponding":false},{"id":370753,"name":"Martin Sjöström","orcid":"0000-0002-2629-9966","position":26,"is_corresponding":false},{"id":885631,"name":"Marina N. Sharifi","orcid":"0000-0003-0128-3033","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-19T02:52:16.891390Z","pmid":"39985777","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":[]}