{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:44:03Z","timestamp":1791233043511,"version":"4.1.0"},"reference-count":45,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T00:00:00Z","timestamp":1647388800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003359","name":"Generalitat Valenciana","doi-asserted-by":"publisher","award":["Prometeo II\/2015\/009"],"award-info":[{"award-number":["Prometeo II\/2015\/009"]}],"id":[{"id":"10.13039\/501100003359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI17\/02019"],"award-info":[{"award-number":["PI17\/02019"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI20\/00094"],"award-info":[{"award-number":["PI20\/00094"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"FEDER European funds","award":["PI17\/02019"],"award-info":[{"award-number":["PI17\/02019"]}]},{"name":"FEDER European funds","award":["PI20\/00094"],"award-info":[{"award-number":["PI20\/00094"]}]},{"DOI":"10.13039\/501100002704","name":"Asociaci\u00f3n Espa\u00f1ola Contra el C\u00e1ncer","doi-asserted-by":"publisher","award":["Donation Proyecto Everest"],"award-info":[{"award-number":["Donation Proyecto Everest"]}],"id":[{"id":"10.13039\/501100002704","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>BRAF mutations are present in around 50% of cutaneous malignant melanomas and are related to a poor outcome in advanced-stage melanoma patients. miRNAs are epigenetic regulators that modulate different cellular processes in cancer, including melanoma development and progression. However, there are no studies on the potential associations of the genetic alterations of the BRAF gene with miRNA expression in primary cutaneous melanomas. Here, in order to analyze the influence of BRAF mutations in the ability of selected miRNAs to predict clinical outcome and patient survival at the time of diagnosis, we studied the prognostic value of miR-125b, miR-200c and miR-205 expression depending on the BRAF mutational status in fresh, frozen primary tumor specimens. For this purpose, RNA was extracted for studying both BRAF mutations by Sanger sequencing and miRNA expression. Our results indicate that, although there seems to be a slight preference for their predictive ability in the BRAF mutated group, the expression of these three miRNAs serves effectively to predict the clinical outcome of melanoma patients independently of BRAF mutational status at the time of primary tumor diagnosis.<\/jats:p>","DOI":"10.3390\/cancers14061532","type":"journal-article","created":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T22:09:58Z","timestamp":1647468598000},"page":"1532","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Prognostic Value of miR-125b, miR-200c and miR-205 in Primary Cutaneous Malignant Melanoma Is Independent of BRAF Mutational Status"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9115-9249","authenticated-orcid":false,"given":"Beatriz","family":"S\u00e1nchez-Sendra","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Valencia, 46010 Valencia, Spain"},{"name":"Biomedical Research Institute INCLIVA, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9832-3355","authenticated-orcid":false,"given":"Jos\u00e9 F.","family":"Gonz\u00e1lez-Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute INCLIVA, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"P\u00e9rez-Deb\u00e9n","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute INCLIVA, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9381-9976","authenticated-orcid":false,"given":"Carlos","family":"Monteagudo","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Valencia, 46010 Valencia, Spain"},{"name":"Biomedical Research Institute INCLIVA, 46010 Valencia, Spain"},{"name":"Department of Pathology, Hospital Cl\u00ednico Universitario de Valencia, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.ejca.2019.11.014","article-title":"European consensus-based interdisciplinary guideline for melanoma. Part 1: Diagnostics\u2014Update 2019","volume":"126","author":"Garbe","year":"2020","journal-title":"Eur. J. Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21590","article-title":"Cancer statistics, 2020","volume":"70","author":"Siegel","year":"2020","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"472","DOI":"10.3322\/caac.21409","article-title":"Melanoma staging: Evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual","volume":"67","author":"Gershenwald","year":"2017","journal-title":"CA Cancer J. Clin."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2149","DOI":"10.1101\/gad.1437206","article-title":"Malignant melanoma: Genetics and therapeutics in the genomic era","volume":"20","author":"Chin","year":"2006","journal-title":"Genes Dev."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Lovly, C.M., Dahlman, K.B., Fohn, L.E., Su, Z., Dias-Santagata, D., Hicks, D.J., Hucks, D., Berry, E., Terry, C., and Duke, M. (2012). Routine multiplex mutational profiling of melanomas enables enrollment in genotype-driven therapeutic trials. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0035309"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1002\/cncr.30593","article-title":"Somatic driver mutations in melanoma","volume":"123","author":"Reddy","year":"2017","journal-title":"Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3490","DOI":"10.1002\/cncr.31345","article-title":"Melanoma: What do all the mutations mean?","volume":"124","author":"Davis","year":"2018","journal-title":"Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e25594","DOI":"10.4161\/onci.25594","article-title":"Biological insights into BRAFV600 mutations in melanoma patient: Not mere therapeutic targets","volume":"2","author":"Improta","year":"2013","journal-title":"Oncoimmunology"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Revythis, A., Shah, S., Kutka, M., Moschetta, M., Ozturk, M.A., Pappas-Gogos, G., Ioannidou, E., Sheriff, M., Rassy, E., and Boussios, S. (2021). Unraveling the wide spectrum of melanoma biomarkers. Diagnostics, 11.","DOI":"10.3390\/diagnostics11081341"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1038\/jid.2012.283","article-title":"BRAF mutation, NRAS mutation, and the absence of an immune-related expressed gene profile predict poor outcome in patients with stage III melanoma","volume":"133","author":"Mann","year":"2013","journal-title":"J. Investig. Dermatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1177\/1535370220959657","article-title":"Prevalence of class I-III BRAF mutations among 114,662 cancer patients in a large genomic database","volume":"246","author":"Owsley","year":"2021","journal-title":"Exp. Biol. Med."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Louveau, B., Jouenne, F., Reger de Moura, C., Sadoux, A., Baroudjian, B., Delyon, J., Herms, F., De Masson, A., Da Meda, L., and Battistella, M. (2019). Baseline genomic features in BRAFV600-mutated metastatic melanoma patients treated with BRAF inhibitor + MEK inhibitor in routine care. Cancers, 11.","DOI":"10.3390\/cancers11081203"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S0092-8674(04)00045-5","article-title":"MicroRNAs: Genomics, biogenesis, mechanism, and function","volume":"116","author":"Bartel","year":"2004","journal-title":"Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1038\/nature03702","article-title":"MicroRNA expression profiles classify human cancers","volume":"435","author":"Lu","year":"2005","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1080\/15592294.2014.1003746","article-title":"Epigenetic regulation in human melanoma: Past and future","volume":"10","author":"Sarkar","year":"2015","journal-title":"Epigenetics"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.ejca.2015.10.009","article-title":"MicroRNAs as potential diagnostic and prognostic biomarkers in melanoma","volume":"53","author":"Mirzaei","year":"2016","journal-title":"Eur. J. Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.suronc.2016.05.017","article-title":"MicroRNA dysregulation in melanoma","volume":"25","author":"Latchana","year":"2016","journal-title":"Surg. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"17076","DOI":"10.1038\/s41598-018-35317-3","article-title":"Downregulation of intratumoral expression of miR-205, miR-200c and miR-125b in primary human cutaneous melanomas predicts shorter survival","volume":"8","author":"Murgui","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0092-8674(00)81683-9","article-title":"The hallmarks of cancer","volume":"100","author":"Hanahan","year":"2000","journal-title":"Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1152\/physiolgenomics.00116.2013","article-title":"miR in melanoma development: miRNAs and acquired hallmarks of cancer in melanoma","volume":"45","author":"Bennett","year":"2013","journal-title":"Physiol. Genomics"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1080\/14728222.2019.1554057","article-title":"The potential of BRAF-associated non-coding RNA as a therapeutic target in melanoma","volume":"23","author":"Fattore","year":"2019","journal-title":"Expert. Opin. Ther. Targets"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1038\/onc.2012.209","article-title":"Oncogenic B-Raf signaling in melanoma cells controls a network of microRNAs with combinatorial functions","volume":"32","author":"Couts","year":"2013","journal-title":"Oncogene"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1080\/15476286.2019.1600934","article-title":"Systematic evaluation of the microRNAome through miR-CATCHv2.0 identifies positive and negative regulators of BRAF-X1 mRNA","volume":"16","author":"Marranci","year":"2019","journal-title":"RNA Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2062","DOI":"10.1038\/jid.2010.63","article-title":"MicroRNA expression profiles associated with mutational status and survival in malignant melanoma","volume":"130","author":"Caramuta","year":"2010","journal-title":"J. Investig. Dermatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4085","DOI":"10.21873\/anticanres.13566","article-title":"miRNAs as Potential Prognostic Biomarkers for Metastasis in Thin and Thick Primary Cutaneous Melanomas","volume":"39","author":"Valentini","year":"2019","journal-title":"Anticancer Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1517\/14728222.2015.1065818","article-title":"MicroRNA expression in BRAF-mutated and wild-type metastatic melanoma and its correlation with response duration to BRAF inhibitors","volume":"19","author":"Pinto","year":"2015","journal-title":"Expert. Opin. Ther. Targets"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Zaman, A., Wu, W., and Bivona, T.G. (2019). Targeting oncogenic BRAF: Past, present and future. Cancers, 11.","DOI":"10.3390\/cancers11081197"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Khaliq, M., and Fallahi-Sichani, M. (2019). Epigenetic mechanisms of escape from BRAF oncongene dependency. Cancers, 11.","DOI":"10.3390\/cancers11101480"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/bjc.2014.476","article-title":"Beyond BRAF: Where next for melanoma therapy?","volume":"112","author":"Fedorenko","year":"2015","journal-title":"Br. J. Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e13270","DOI":"10.1111\/dth.13270","article-title":"BRAF V600E mutations as a prognostic factor in cutaneous melanoma patients","volume":"33","author":"Tas","year":"2020","journal-title":"Dermatol. Ther."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Heppt, M.V., Siepmann, T., Engel, J., Schubert-Fritschle, G., Eckel, R., Mirlach, L., Kirchner, T., Jung, A., Gesierich, A., and Ruzicka, T. (2017). Prognostic significance of BRAF and NRAS mutations in melanoma: A German study from routine care. BMC Cancer, 17.","DOI":"10.1186\/s12885-017-3529-5"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1111\/bjd.13756","article-title":"The role of BRAF mutations in primary melanoma growth rate and survival","volume":"173","author":"Mar","year":"2015","journal-title":"Br. J. Dermatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1111\/j.0022-202X.2005.23788.x","article-title":"BRAF and NRAS mutations are frequent in nodular melanoma but are not associated with tumor cell proliferation or patient survival","volume":"125","author":"Akslen","year":"2005","journal-title":"J. Investig. Dermatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1158\/1078-0432.CCR-1169-3","article-title":"Incidence of BRAF oncogene mutation and clinical relevance for primary cutaneous melanomas","volume":"10","author":"Shinozaki","year":"2004","journal-title":"Clin. Cancer Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.semcancer.2019.05.021","article-title":"MicroRNA heterogeneity in melanoma progression","volume":"59","author":"Thyagarajan","year":"2019","journal-title":"Semin. Cancer Biol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Varrone, F., and Caputo, E. (2020). The miRNAs Role in Melanoma and in Its Resistance to Therapy. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21030878"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.canlet.2019.04.015","article-title":"MicroRNA-125 in immunity and cancer","volume":"454","author":"Wang","year":"2019","journal-title":"Cancer Lett."},{"key":"ref_39","first-page":"1856","article-title":"Association between microRNA-125b expression in formalin-fixed paraffin-embedded tumor tissues and prognosis in patients with melanoma","volume":"18","author":"Yan","year":"2019","journal-title":"Oncol. Lett."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4428","DOI":"10.18632\/oncotarget.6599","article-title":"Overcoming melanoma resistance to vemurafenib by targeting CCL2-induced miR-34a, miR-100 and miR-125b","volume":"7","author":"Vergani","year":"2016","journal-title":"Oncotarget"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Lorusso, C., De Summa, S., Pinto, R., Danza, K., and Tommasi, S. (2020). miRNAs as Key Players in the Management of Cutaneous Melanoma. Cells, 9.","DOI":"10.3390\/cells9020415"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1186\/1479-5876-11-218","article-title":"MicroRNAs induced in melanoma treated with combination targeted therapy of Temsirolimus and Bevacizumab","volume":"18","author":"Wagenseller","year":"2013","journal-title":"J. Transl. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"5133","DOI":"10.1002\/jcp.26395","article-title":"MicroRNAs in cutaneous melanoma: Role as diagnostic and prognostic biomarkers","volume":"233","author":"Ross","year":"2018","journal-title":"J. Cell Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1097\/CMR.0b013e32833e32a1","article-title":"Downregulation of miR-125b in metastatic cutaneous malignant melanoma","volume":"20","author":"Glud","year":"2010","journal-title":"Melanoma Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1038\/bjc.2011.568","article-title":"Differential expression of microRNAs during melanoma progression: miR-200c, miR-205 and miR-211 are downregulated in melanoma and act as tumour suppressors","volume":"106","author":"Xu","year":"2012","journal-title":"Br. J. Cancer"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/6\/1532\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:37:49Z","timestamp":1760135869000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/6\/1532"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,16]]},"references-count":45,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["cancers14061532"],"URL":"https:\/\/doi.org\/10.3390\/cancers14061532","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,16]]}}}