{"doi":"10.1016/j.neo.2025.101151","title":"LSD1+8a is an RNA biomarker of neuroendocrine prostate cancer","abstract":"BACKGROUND: Lysine-specific demethylase 1 (LSD1) is a histone demethylase and regulator of differentiation, including in cancer. A neuronal-specific isoform of LSD1-LSD1+8a-has been shown to play a key role in promoting neuronal differentiation in the developing brain. We previously determined that LSD1+8a transcripts were detected in an aggressive subtype of prostate cancer harboring a neuronal program-neuroendocrine prostate cancer (NEPC)-but not in prostate adenocarcinomas harboring a glandular program. However, the number of samples examined was limited. METHODS: Using a large collection of prostate cancer patient cell lines and patient-derived xenografts (PDXs), we measured LSD1+8a using quantitative polymerase chain reaction (qPCR), RNA in situ hybridization (RNA-ISH), and protein detection methods. We then validated our findings using an independent cohort of patient tumor samples. RESULTS: LSD1+8a mRNA expression was detected in every NEPC cell line and PDX examined by qPCR and RNA-ISH but in none of the prostate adenocarcinomas. We validated the RNA-ISH results in patient tumors, confirming that LSD1+8a was expressed in all NEPC tumors but in none of the adenocarcinomas. Finally, we generated a rabbit monoclonal antibody specific to LSD1+8a protein and confirmed its specificity using normal neuronal tissue samples. However, LSD1+8a protein was not detectable in NEPC tumors-likely due to the substantially lower levels of LSD1+8a mRNA in NEPC tumors vs. normal neuronal tissues. CONCLUSIONS: Measuring LSD1+8a mRNA is a sensitive and specific method for the diagnosis of NEPC, which is often challenging.","journal":"Neoplasia","year":2025,"id":552024,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"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":0.9676,"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":108220,"name":"Rahul Mannan","orcid":"0000-0002-6642-0468","position":1,"is_corresponding":false},{"id":1382505,"name":"Olivia A Swaim","orcid":"0009-0004-8573-5440","position":2,"is_corresponding":false},{"id":1383079,"name":"Eva S. Rodansky","orcid":null,"position":3,"is_corresponding":false},{"id":379360,"name":"Xiaoming Wang","orcid":"0000-0002-9671-6358","position":4,"is_corresponding":false},{"id":582192,"name":"Aaron M. Udager","orcid":"0000-0002-8254-5404","position":5,"is_corresponding":false},{"id":64720,"name":"Rohit Mehra","orcid":null,"position":6,"is_corresponding":false},{"id":1447931,"name":"Hui Li","orcid":"0000-0001-7145-4681","position":7,"is_corresponding":false},{"id":291423,"name":"Colm Morrissey","orcid":"0000-0003-1906-5333","position":8,"is_corresponding":false},{"id":291421,"name":"Eva Corey","orcid":"0000-0002-9244-3807","position":9,"is_corresponding":false},{"id":1167048,"name":"Michael Haffner","orcid":"0000-0001-9906-6832","position":10,"is_corresponding":false},{"id":255746,"name":"Peter S. Nelson","orcid":"0000-0002-5451-5726","position":11,"is_corresponding":false},{"id":51796,"name":"Arul M. Chinnaiyan","orcid":"0000-0001-9282-3415","position":12,"is_corresponding":false},{"id":289065,"name":"Joel A. Yates","orcid":"0000-0002-1462-8494","position":13,"is_corresponding":false},{"id":370757,"name":"Joshi J. Alumkal","orcid":"0000-0003-1278-0166","position":14,"is_corresponding":false},{"id":490948,"name":"Anbarasu Kumaraswamy","orcid":"0000-0002-9997-7430","position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:54:29.318076Z","pmid":"40088674","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":[]}