{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T10:24:33Z","timestamp":1781173473883,"version":"3.54.1"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T00:00:00Z","timestamp":1743638400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T00:00:00Z","timestamp":1743638400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universit\u00e4tsklinikum Hamburg-Eppendorf (UKE)"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Exp Clin Cancer Res"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Purpose<\/jats:title>\n            <jats:p>New biomarkers for the detection and monitoring of aggressive variant prostate cancer (AVPC) including therapy-induced neuroendocrine prostate cancer (NEPC) are urgently needed, as measuring prostate-specific antigen (PSA) is not reliable in androgen-indifferent diseases. Molecular analysis of circulating tumor cells (CTC) enables repeated analysis for monitoring and allows to capture the heterogeneity of the disease.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Experimental design<\/jats:title>\n            <jats:p>102 blood samples from 76 metastatic prostate cancer (mPC) patients, including 37 samples from histologically proven NEPC, were collected and CTCs were enriched using label-dependent and label-independent methods. Relevant transcripts were selected for CTC profiling using semi-quantitative RT-PCR analysis and validated in published datasets and cell lines. Transcriptional profiles in patient samples were analyzed using supervised and unsupervised methods.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>CTC counts were increased in AVPC and NEPC as compared to metastatic hormone-sensitive prostate cancer (mHSPC). Gene expression profiles of CTCs showed a high degree of inter-patient heterogeneity, but NEPC-specific transcripts were significantly increased in patients with proven NEPC, while adenocarcinoma markers were decreased. Unsupervised analysis identified four distinct clusters of CTC<jats:sup>low<\/jats:sup>, AR<jats:sup>high<\/jats:sup>, amphicrine and pure NEPC gene expression profiles that reflected the clinical groups. Based on the transcript panel, NEPC could be distinguished from mHSPC or AVPC patients with a specificity of 95.5% and 88.2%, respectively.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Molecular subtypes of mPC can be distinguished by transcriptional profiling of CTCs. In the future, our convenient PCR-based analysis may complement the monitoring of advanced PCa patients and allow timely detection of resistance to androgen receptor pathway inhibitors.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s13046-025-03367-x","type":"journal-article","created":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T07:47:13Z","timestamp":1743752833000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Transcriptional profiles of circulating tumor cells reflect heterogeneity and treatment resistance in advanced prostate cancer"],"prefix":"10.1186","volume":"44","author":[{"given":"Lina","family":"Bergmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Greimeier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Riethdorf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Rohlfing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moritz","family":"Kaune","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Busenbender","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadja","family":"Strewinsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey","family":"Dyshlovoy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Joosse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Peine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Pantel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunhild","family":"von Amsberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Werner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,3]]},"reference":[{"issue":"4","key":"3367_CR1","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1038\/nrc2351","volume":"8","author":"H Lilja","year":"2008","unstructured":"Lilja H, Ulmert D, Vickers AJ. 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All patients gave informed consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors read and approved the final manuscript.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Gunhild von Amsberg is consultant or advisor of Amgen, Roche, BMS, Astellas, Sanofi, Janssen, MSD, Ipsen, Pfizer, AstraZeneca, Merck, EISAI, Bayer. The other authors declare no potential conflicts of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Blood-based biomarkers of metastatic prostate cancer are urgently needed to identify patients with progression to aggressive and androgen-independent disease, and to monitor treatment response and emerging therapy resistance. We have developed a convenient PCR-based method to identify neuroendocrine prostate cancers based on their gene expression in circulating tumor cells. This test allows clinical monitoring of patients under androgen receptor-directed treatment and enables the early identification of progression to androgen-independent and therapy-induced neuroendocrine prostate cancer. In this way, suitable treatment strategies can be applied at an early stage before clinical symptoms and deterioration of general condition have occurred.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Statement of translational relevance"}}],"article-number":"111"}}