{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T08:10:03Z","timestamp":1791706203735,"version":"4.3.4"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T00:00:00Z","timestamp":1738281600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T00:00:00Z","timestamp":1738281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100007837","name":"Universit\u00e4t Bremen","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007837","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Cancer Res Clin Oncol"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Purpose<\/jats:title>\n            <jats:p>microRNA-371a-3p (M371) is considered a highly sensitive and specific serum biomarker of testicular germ cell tumours (GCTs). However, little is known about the expression of M371 in nontesticular malignancies (NTMs), so far. As knowledge about the expression of the marker in other malignancies is a prerequisite for the clinical application of the test we aimed to explore the M371 expression in other cancers.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>M371 serum levels were measured in 137 patients with NTM of 12 different neoplastic entities using the IVDR-certified M371-Test for quantitative real-time PCR. Median M371 serum levels and percentages of M371 level elevations were calculated for the entire NTM group and for entity-specific subgroups. The results were compared with GCT patients (<jats:italic>n<\/jats:italic>\u2009=\u200920) and with tumour-free male controls (<jats:italic>n<\/jats:italic>\u2009=\u200920) using descriptive statistical methods.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Eight patients with NTMs had M371 serum level elevations, corresponding to a false-positive rate (FPR) of 5.84% (95% confidence intervals (CIs) 2.55\u201311.18%). Expression rates in GCTs and controls were 100% and zero, respectively. Thus, the specificity of the M371-Test for GCT is 94.90% (95% CI 90.21\u201397.77%) when all NTMs and tumour-free controls are considered. Remarkably, three out of 5 patients with multiple myeloma had elevated M371 levels.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>The false-positive rate of the M371-Test in other malignancies than GCT is very low, and almost identical with that in healthy males, corresponding to a high specificity of 94.9% for detection of GCT. The surprising finding of M371 elevations in patients with multiple myeloma needs further investigation.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s00432-025-06101-4","type":"journal-article","created":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T07:30:38Z","timestamp":1738308638000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Biomarker microRNA-371a-3p - expression in malignancies other than germ-cell tumours"],"prefix":"10.1007","volume":"151","author":[{"given":"Gazanfer","family":"Belge","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Klemke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bendix","family":"Hansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cansu","family":"Dumlupinar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aylin","family":"Igde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Arnold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Salwender","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"W\u00fclfing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armin","family":"Soave","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus-Peter","family":"Dieckmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,31]]},"reference":[{"key":"6101_CR2","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1007\/s00432-020-03429-x","volume":"147","author":"G Belge","year":"2020","unstructured":"Belge G, Grobelny F, Radtke A, Bodes J, Matthies C, W\u00fclfing C, Dieckmann KP (2020) Serum levels of microRNA-371a-3p are not elevated in testicular tumours of non-germ cell origin. J Cancer Res Clin Oncol 147:435\u2013443","journal-title":"J Cancer Res Clin Oncol"},{"key":"6101_CR1","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1158\/1078-0432.CCR-23-0730","volume":"30","author":"G Belge","year":"2024","unstructured":"Belge G, Dumlupinar C, Nestler T, Klemke M, T\u00f6rzs\u00f6k P, Trenti E, Pichler R, Loidl W, Che Y, Hiester A, Matthies C, Pichler M, Paffenholz P, Kluth L, Wenzel M, Sommer J, Heinzelbecker J, Schriefer P, Winter A, Zengerling F, Kramer MW, Lengert M, Frey J, Heidenreich A, W\u00fclfing C, Radtke A, Dieckmann KP (2024) Detection of recurrence through microRNA-371a-3p serum levels in a follow-up of stage I testicular germ cell tumors in the DRKS-00019223 study. Clin Cancer Res 30:404\u2013412","journal-title":"Clin Cancer Res"},{"key":"6101_CR3","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1159\/000478706","volume":"99","author":"KP Dieckmann","year":"2017","unstructured":"Dieckmann KP, Anheuser P, Simonsen H, H\u00f6flmayer D (2017a) Pure testicular seminoma with non-pathologic elevation of alpha fetoprotein: a Case Series. Urol Int 99:353\u2013357","journal-title":"Urol Int"},{"key":"6101_CR4","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/j.eururo.2016.07.029","volume":"71","author":"KP Dieckmann","year":"2017","unstructured":"Dieckmann KP, Radke A, Spiekermann M, Balks T, Matthies C, Becker P, Ruf C, Oing C, Oechsle K, Bokemeyer C, Hammel J, Melchior S, Wosniok W, Belge G (2017b) Serum levels of MicroRNA 371a-3p: a sensitive and specific new biomarker for germ cell tumors. Eur Urol 71:213\u2013220","journal-title":"Eur Urol"},{"key":"6101_CR5","doi-asserted-by":"publisher","first-page":"1412","DOI":"10.1200\/JCO.18.01480","volume":"37","author":"KP Dieckmann","year":"2019","unstructured":"Dieckmann KP, Radtke A, Geczi L, Matthies C, Anheuser P, Eckardt U, Sommer J, Zengerling F, Trenti E, Pichler R, Belz H, Zastrow S, Winter A, Melchior S, Hammel J, Kranz J, Bolten M, Krege S, Haben B, Loidl W, Ruf CG, Heinzelbecker J, Heidenreich A, Cremers JF, Oing C, Hermanns T, Fankhauser CD, Gillessen S, Reichegger H, Cathomas R, Pichler M, Hentrich M, Eredics K, Lorch A, W\u00fclfing C, Peine S, Wosniok W, Bokemeyer C, Belge G (2019) Serum levels of microRNA-371a-3p (M371 test) as a new biomarker of testicular germ cell-tumors: results of a prospective multicentric study. J Clin Oncol 37:1412\u20131423","journal-title":"J Clin Oncol"},{"key":"6101_CR6","doi-asserted-by":"publisher","first-page":"1140","DOI":"10.1038\/s41416-021-01643-z","volume":"126","author":"CD Fankhauser","year":"2022","unstructured":"Fankhauser CD, Christiansen AJ, Rothermundt C, Cathomas R, Wettstein MS, Grossmann NC, Grogg JB, Templeton AJ, Hirschi-Blickenstorfer A, Lorch A, Gillessen S, Moch H, Beyer J, Hermanns T (2022) Detection of recurrences using serum miR-371a-3p during active surveillance in men with stage I testicular germ cell tumours. Br J Cancer 126:1140\u20131144","journal-title":"Br J Cancer"},{"key":"6101_CR7","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.canlet.2018.11.021","volume":"443","author":"H Guo","year":"2019","unstructured":"Guo H, Ji F, Zhao X, Yang X, He J, Huang L, Zhang Y (2019) MicroRNA-371a-3p promotes progression of gastric cancer by targeting TOB1. Cancer Lett 443:179\u2013188","journal-title":"Cancer Lett"},{"key":"6101_CR8","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1016\/j.eururo.2019.10.005","volume":"77","author":"JT Lafin","year":"2020","unstructured":"Lafin JT, Singla N, Woldu SL, Lotan Y, Lewis CM, Majmudar K, Savelyeva A, Kapur P, Margulis V, Strand DW, Murray MJ, Amatruda JF, Bagrodia A (2020) Serum MicroRNA-371a-3p levels predict viable germ cell tumor in Chemotherapy-na\u00efve patients undergoing Retroperitoneal Lymph Node Dissection. Eur Urol 77:290\u2013292","journal-title":"Eur Urol"},{"key":"6101_CR9","doi-asserted-by":"publisher","first-page":"2490","DOI":"10.1182\/blood.V85.9.2490.bloodjournal8592490","volume":"85","author":"JL La\u00ef","year":"1995","unstructured":"La\u00ef JL, Zandecki M, Mary JY, Bernardi F, Izydorczyk V, Flactif M, Morel P, Jouet JP, Bauters F, Facon T (1995) Improved cytogenetics in multiple myeloma: a study of 151 patients including 117 patients at diagnosis. Blood 85:2490\u20132497","journal-title":"Blood"},{"key":"6101_CR10","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1002\/1097-0142(19870801)60:3+<464::AID-CNCR2820601506>3.0.CO;2-C","volume":"60","author":"PH Lange","year":"1987","unstructured":"Lange PH, Winfield HN (1987) Biological markers in urologic cancer. Cancer 60:464\u2013472","journal-title":"Cancer"},{"key":"6101_CR11","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1159\/000535497","volume":"13","author":"L Lani","year":"2024","unstructured":"Lani L, Stefanini B, Trevisani F (2024) Surveillance for Hepatocellular Carcinoma in patients with successfully treated viral disease of the liver: a systematic review. Liver Cancer 13:376\u2013388","journal-title":"Liver Cancer"},{"key":"6101_CR12","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1016\/j.eururo.2021.06.006","volume":"80","author":"R Le\u00e3o","year":"2021","unstructured":"Le\u00e3o R, Albersen M, Looijenga LHJ, Tandstad T, Kollmannsberger C, Murray MJ, Culine S, Coleman N, Belge G, Hamilton RJ, Dieckmann KP (2021) Circulating MicroRNAs, the Next-Generation serum biomarkers in testicular germ cell tumours: a systematic review. Eur Urol 80:456\u2013466","journal-title":"Eur Urol"},{"key":"6101_CR13","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","volume":"25","author":"KJ Livak","year":"2001","unstructured":"Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25:402\u2013408","journal-title":"Methods"},{"key":"6101_CR14","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1016\/j.euo.2020.11.004","volume":"4","author":"J Lobo","year":"2021","unstructured":"Lobo J, Le\u00e3o R, Gillis AJM, van den Berg A, Anson-Cartwright L, Atenafu EG, Kuhathaas K, Chung P, Hansen A, Bedard PL, Jewett MAS, Warde P, O\u2019Malley M, Sweet J, Looijenga LHJ, Hamilton RJ (2021) Utility of serum miR-371a-3p in Predicting Relapse on Surveillance in patients with clinical stage I testicular germ cell Cancer. Eur Urol Oncol 4:483\u2013491","journal-title":"Eur Urol Oncol"},{"key":"6101_CR15","doi-asserted-by":"publisher","first-page":"1080","DOI":"10.1002\/ajh.20998","volume":"82","author":"AN Mohamed","year":"2007","unstructured":"Mohamed AN, Bentley G, Bonnett ML, Zonder J, Al-Katib A (2007) Chromosome aberrations in a series of 120 multiple myeloma cases with abnormal karyotypes. Am J Hematol 82:1080\u20131087","journal-title":"Am J Hematol"},{"key":"6101_CR16","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1046\/j.1365-2141.2003.04221.x","volume":"120","author":"T Nilsson","year":"2003","unstructured":"Nilsson T, H\u00f6glund M, Lenhoff S, Rylander L, Turesson I, Westin J, Mitelman F, Johansson B (2003) A pooled analysis of karyotypic patterns, breakpoints and imbalances in 783 cytogenetically abnormal multiple myelomas reveals frequently involved chromosome segments as well as significant age- and sex-related differences. Br J Haematol 120:960\u2013699","journal-title":"Br J Haematol"},{"key":"6101_CR17","doi-asserted-by":"publisher","first-page":"103224","DOI":"10.1016\/j.critrevonc.2021.103224","volume":"159","author":"P Pedrazzoli","year":"2021","unstructured":"Pedrazzoli P, Rosti G, Soresini E, Ciani S, Secondino S (2021) Serum tumour markers in germ cell tumours: from diagnosis to cure. Crit Rev Oncol Hematol 159:103224","journal-title":"Crit Rev Oncol Hematol"},{"key":"6101_CR18","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1159\/000488771","volume":"100","author":"A Radtke","year":"2018","unstructured":"Radtke A, Hennig F, Ikogho R, Hammel J, Anheuser P, W\u00fclfing C, Belge G, Dieckmann KP (2018) The Novel Biomarker of Germ Cell Tumours, Micro-RNA-371a-3p, has a very Rapid Decay in patients with clinical stage 1. Urol int 100:470\u2013475","journal-title":"Urol int"},{"key":"6101_CR19","doi-asserted-by":"publisher","first-page":"e9485","DOI":"10.1371\/journal.pone.0009485","volume":"5","author":"V Rippe","year":"2010","unstructured":"Rippe V, Dittberner L, Lorenz VN, Drieschner N, Nimzyk R, Sendt W, Junker K, Belge G, Bullerdiek J (2010) The two stem cell MicroRNA gene clusters C19MC and mir-371-3 are activated by specific chromosomal rearrangements in a subgroup of thyroid adenomas. PlosOne PLoS One 5:e9485","journal-title":"PlosOne PLoS One"},{"key":"6101_CR20","doi-asserted-by":"publisher","first-page":"1379","DOI":"10.3390\/cancers16071379","volume":"16","author":"CL Seales","year":"2024","unstructured":"Seales CL, Puri D, Yodkhunnatham N, Pandit K, Yuen K, Murray S, Smitham J, Lafin JT, Bagrodia A (2024) Advancing GCT management: a review of miR-371a-3p and other miRNAs in comparison to traditional serum tumor markers. Cancers (Basel) 16:1379","journal-title":"Cancers (Basel)"},{"key":"6101_CR21","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/j.euo.2023.10.021","volume":"7","author":"F Seelemeyer","year":"2024","unstructured":"Seelemeyer F, Pfister D, Pappesch R, Merkelbach-Bruse S, Paffenholz P, Heidenreich A (2024) Evaluation of a miRNA-371a-3p assay for Predicting final histopathology in patients undergoing primary nerve-sparing Retroperitoneal Lymphadenectomy for Stage IIA\/B Seminoma or Nonseminoma. Eur Urol Oncol 7:319\u2013322","journal-title":"Eur Urol Oncol"},{"key":"6101_CR22","first-page":"984","volume":"11","author":"JA Shah","year":"2021","unstructured":"Shah JA, Khattak S, Rauf MA, Cai Y, Jin J (2021) Potential biomarkers of mir-371-373 gene cluster in Tumorigenesis. Life (Basel) 11:984","journal-title":"Life (Basel)"},{"key":"6101_CR23","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1111\/j.2047-2927.2014.00269.x","volume":"3","author":"M Spiekermann","year":"2015","unstructured":"Spiekermann M, Belge G, Winter N, Ikogho R, Balks T, Bullerdiek J, Dieckmann KP (2015) MicroRNA miR-371a-3p in serum of patients with germ cell tumours: evaluations for establishing a serum biomarker. Andrology 3:78\u201384","journal-title":"Andrology"},{"key":"6101_CR24","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/j.juro.2014.07.010","volume":"193","author":"I Syring","year":"2015","unstructured":"Syring I, Bartels J, Holdenrieder S, Kristiansen G, M\u00fcller SC, Ellinger J (2015) Circulating serum microRNA (miR-367-3p, miR-371a-3p, miR-372-3p, miR-373-3p) as biomarkers for patients with testicular germ cell cancers. J Urol 193:331\u2013337","journal-title":"J Urol"},{"key":"6101_CR25","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1007\/s00432-017-2520-5","volume":"144","author":"A Takizawa","year":"2017","unstructured":"Takizawa A, Kawai K, Kawahara T, Kojima T, Maruyama S, Shinohara N, Akamatsu S, Kamba T, Nakamura T, Ukimura O, Jikuya R, Kishida T, Kakimoto K, Nishimura K, Harabayashi T, Nagamori S, Yamashita S, Arai Y, Sawada Y, Sekido N, Kinoshita H, Matsuda T, Nakagawa T, Homma Y, Nishiyama H (2017) The usefulness of testosterone administration in identifying false-positive elevation of serum human chorionic gonadotropin in patients with germ cell tumor. J Cancer Res Clin Oncol 144:109\u2013115","journal-title":"J Cancer Res Clin Oncol"},{"key":"6101_CR26","doi-asserted-by":"publisher","first-page":"58037","DOI":"10.18632\/oncotarget.10867","volume":"8","author":"T van Agthoven","year":"2017","unstructured":"van Agthoven T, Looijenga LH (2017) Accurate primary germ cell cancer diagnosis using serum based microRNA detection (ampTSmiR test). Oncotarget 8:58037\u201358049","journal-title":"Oncotarget"},{"key":"6101_CR27","first-page":"760","volume":"35","author":"J Wang","year":"2020","unstructured":"Wang J, Dong S, Zhang J, Jing D, Wang W, Dong L, Zhao Y (2020) LncRNA NR2F1-AS1 regulates miR-371a-3p\/TOB1 Axis to suppress proliferation of Colorectal Cancer cells. Cancer Biother Radiopharm 35:760\u2013764","journal-title":"Cancer Biother Radiopharm"}],"container-title":["Journal of Cancer Research and Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00432-025-06101-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00432-025-06101-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00432-025-06101-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T21:24:11Z","timestamp":1741814651000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00432-025-06101-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,31]]},"references-count":27,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["6101"],"URL":"https:\/\/doi.org\/10.1007\/s00432-025-06101-4","relation":{},"ISSN":["1432-1335"],"issn-type":[{"value":"1432-1335","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,31]]},"assertion":[{"value":"2 December 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 January 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 January 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the The Ethical Committee of \u00c4rztekammer Bremen (HR\/RE-301A).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Klaus-Peter Dieckmann and Gazanfer Belge possess 5.7% ownership shares of mir|detect Company, Bremerhaven, Germany. Markus Klemke is employee of mir|detect Company, Bremerhaven, Germany. All other authors declare they have no conflicts of interest with publishing this article.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"58"}}