{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,13]],"date-time":"2025-04-13T14:20:21Z","timestamp":1744554021363,"version":"3.37.3"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2019,2,28]],"date-time":"2019-02-28T00:00:00Z","timestamp":1551312000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100014535","name":"Mayo Clinic Center for Individualized Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014535","id-type":"DOI","asserted-by":"publisher"}]},{"name":"People\u2019s Hospital of Zhengzhou University"},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81472835"],"award-info":[{"award-number":["81472835"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,3,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>MCAM (CD146) is a cell surface adhesion molecule that has been reported to promote cancer development, progression and metastasis and is considered as a potential tumor biomarker and therapeutic target. However, inconsistent reports exist, and its clinical value is yet to be confirmed. Here we took advantage of several large genomic data collections (Genotype-Tissue Expression, The Cancer Genome Atlas and Cancer Cell Line Encyclopedia) and comprehensively analyzed MCAM expression in thousands of normal and cancer samples and cell lines along with their clinical phenotypes and drug response information. Our results show that MCAM is very highly expressed in large vessel tissues while majority of tissues have low or minimal expression. Its expression is dramatically increased in a few tumors but significantly decreased in most other tumors relative to their pairing normal tissues. Increased MCAM expression is associated with a higher tumor stage and worse patient survival for some less common tumors but not for major ones. Higher MCAM expression in primary tumors may be complicated by tumor-associated or normal stromal blood vessels yet its significance may differ from the one from cancer cells. MCAM expression is weakly associated with the response to a few small molecular drugs and the association with targeted anti-BRAF agents suggests its involvement in that pathway which warrants further investigation.<\/jats:p>","DOI":"10.1093\/bib\/bbz019","type":"journal-article","created":{"date-parts":[[2019,2,18]],"date-time":"2019-02-18T20:09:07Z","timestamp":1550520547000},"page":"709-718","source":"Crossref","is-referenced-by-count":9,"title":["MCAM abnormal expression and clinical outcome associations are highly cancer dependent as revealed through pan-cancer analysis"],"prefix":"10.1093","volume":"21","author":[{"given":"Yunxia","family":"An","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine, Henan Provincial People\u2019s Hospital, People\u2019s Hospital of Zhengzhou University, Zhengzhou, Henan, China"}]},{"given":"Nan","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, People\u2019s Hospital of Zhengzhou University, Zhengzhou, Henan, China"},{"name":"Academy of Medical Science, Zhengzhou University, Zhengzhou, Henan, China"}]},{"given":"Xiangsong","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Henan Provincial People\u2019s Hospital, People\u2019s Hospital of Zhengzhou University, Zhengzhou, Henan, China"}]},{"given":"Ying","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Henan Provincial People\u2019s Hospital, People\u2019s Hospital of Zhengzhou University, Zhengzhou, Henan, China"}]},{"given":"Haiyang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Henan Provincial People\u2019s Hospital, People\u2019s Hospital of Zhengzhou University, Zhengzhou, Henan, China"}]},{"given":"Jia","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Henan Provincial People\u2019s Hospital, People\u2019s Hospital of Zhengzhou University, Zhengzhou, Henan, China"}]},{"given":"Zhiwei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Henan Provincial People\u2019s Hospital, People\u2019s Hospital of Zhengzhou University, Zhengzhou, Henan, China"}]},{"given":"Zhifu","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA"}]},{"given":"Xiaoju","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Henan Provincial People\u2019s Hospital, People\u2019s Hospital of Zhengzhou University, Zhengzhou, Henan, China"}]}],"member":"286","published-online":{"date-parts":[[2019,2,28]]},"reference":[{"issue":"5","key":"2020080709363652100_ref1","doi-asserted-by":"crossref","first-page":"2631","DOI":"10.1182\/blood-2007-07-099622","article-title":"Specific plasma membrane protein phenotype of culture-amplified and native human bone marrow mesenchymal stem cells","volume":"111","author":"Delorme","year":"2008","journal-title":"Blood"},{"issue":"24","key":"2020080709363652100_ref2","doi-asserted-by":"crossref","first-page":"9891","DOI":"10.1073\/pnas.86.24.9891","article-title":"MUC18, a marker of tumor progression in human melanoma, shows sequence similarity to the neural cell adhesion molecules of the immunoglobulin superfamily","volume":"86","author":"Lehmann","year":"1989","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"6","key":"2020080709363652100_ref3","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1002\/(SICI)1097-0215(19990611)81:6<951::AID-IJC18>3.0.CO;2-V","article-title":"Influence of MUC18\/MCAM\/CD146 expression on human melanoma growth and metastasis in SCID mice","volume":"81","author":"Schlagbauer-Wadl","year":"1999","journal-title":"Int J Cancer"},{"issue":"2","key":"2020080709363652100_ref4","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.canlet.2012.11.049","article-title":"CD146, a multi-functional molecule beyond adhesion","volume":"330","author":"Wang","year":"2013","journal-title":"Cancer Lett"},{"issue":"2","key":"2020080709363652100_ref5","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1002\/jcp.20365","article-title":"Gicerin\/CD146 is involved in neurite extension of NGF-treated PC12 cells","volume":"204","author":"Taira","year":"2010","journal-title":"J Cell Physiol"},{"issue":"5","key":"2020080709363652100_ref6","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1046\/j.1432-0436.1995.5850313.x","article-title":"Expression of gicerin in development, oncogenesis and regeneration of the chick kidney","volume":"58","author":"Takaha","year":"1995","journal-title":"Differentiation"},{"issue":"1","key":"2020080709363652100_ref7","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S0304-3940(99)00256-6","article-title":"Expression of gicerin, a cell adhesion molecule, in the abnormal retina in silver plumage color mutation of Japanese quail (Coturnix japonica)","volume":"266","author":"Tsukamoto","year":"1999","journal-title":"Neurosci Lett"},{"issue":"11","key":"2020080709363652100_ref8","doi-asserted-by":"crossref","first-page":"2330","DOI":"10.1182\/blood-2012-01-406108","article-title":"CD146 is a coreceptor for VEGFR-2 in tumor angiogenesis","volume":"120","author":"Jiang","year":"2012","journal-title":"Blood"},{"issue":"1","key":"2020080709363652100_ref9","doi-asserted-by":"crossref","first-page":"7442","DOI":"10.1038\/s41598-017-06637-7","article-title":"CD146 is required for VEGF-C-induced lymphatic sprouting during lymphangiogenesis","volume":"7","author":"Yan","year":"2017","journal-title":"Sci Rep"},{"issue":"1","key":"2020080709363652100_ref10","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1186\/bcr2215","article-title":"CD146 expression is associated with a poor prognosis in human breast tumors and with enhanced motility in breast cancer cell lines","volume":"11","author":"Zabouo","year":"2009","journal-title":"Breast Cancer Res"},{"key":"2020080709363652100_ref11","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.canlet.2016.11.004","article-title":"MCAM\/CD146 promotes tamoxifen resistance in breast cancer cells through induction of epithelial-mesenchymal transition, decreased ER\u03b1 expression and AKT activation","volume":"386","author":"Liang","year":"2017","journal-title":"Cancer Lett"},{"issue":"4","key":"2020080709363652100_ref12","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1073\/pnas.1111053108","article-title":"CD146, an epithelial-mesenchymal transition inducer, is associated with triple-negative breast cancer","volume":"109","author":"Zeng","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"6","key":"2020080709363652100_ref13","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1007\/s11255-012-0255-4","article-title":"CD146 gene expression in clear cell renal cell carcinoma: a potential marker for prediction of early recurrence after nephrectomy","volume":"44","author":"Feng","year":"2012","journal-title":"Int Urol Nephrol"},{"issue":"6","key":"2020080709363652100_ref14","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1089\/cbr.2012.1426","article-title":"CD146 protein as a marker to predict postoperative liver metastasis in colorectal cancer","volume":"28","author":"Tian","year":"2013","journal-title":"Cancer Biother Radiopharm"},{"issue":"2","key":"2020080709363652100_ref15","doi-asserted-by":"crossref","first-page":"859","DOI":"10.3892\/ol.2014.2227","article-title":"Correlation of CD146 expression and clinicopathological characteristics in esophageal squamous cell carcinoma","volume":"8","author":"Li","year":"2014","journal-title":"Oncol Lett"},{"issue":"29","key":"2020080709363652100_ref16","doi-asserted-by":"crossref","first-page":"4150","DOI":"10.1038\/onc.2017.44","article-title":"The histone demethylase KDM3A, and its downstream target MCAM, promote Ewing Sarcoma cell migration and metastasis","volume":"36","author":"Sechler","year":"2017","journal-title":"Oncogene"},{"key":"2020080709363652100_ref17","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s13046-016-0313-3","article-title":"CD146 promotes metastasis and predicts poor prognosis of hepatocellular carcinoma","volume":"35","author":"Jiang","year":"2016","journal-title":"J Exp Clin Cancer Res"},{"issue":"47","key":"2020080709363652100_ref18","doi-asserted-by":"crossref","first-page":"5781","DOI":"10.1038\/onc.2015.36","article-title":"The membrane protein melanoma cell adhesion molecule (MCAM) is a novel tumor marker that stimulates tumorigenesis in hepatocellular carcinoma","volume":"34","author":"Wang","year":"2015","journal-title":"Oncogene"},{"issue":"5","key":"2020080709363652100_ref19","doi-asserted-by":"crossref","first-page":"6399","DOI":"10.3390\/ijms13056399","article-title":"CD146 expression correlates with epithelial-mesenchymal transition markers and a poor prognosis in gastric cancer","volume":"13","author":"Liu","year":"2012","journal-title":"Int J Mol Sci"},{"issue":"1","key":"2020080709363652100_ref20","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s13277-011-0260-8","article-title":"Identification of CD146 expression, angiogenesis, and lymphangiogenesis as progression, metastasis, and poor-prognosis related markers for gallbladder adenocarcinoma","volume":"33","author":"Wang","year":"2012","journal-title":"Tumour Biol"},{"issue":"1","key":"2020080709363652100_ref21","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/s40001-015-0160-2","article-title":"CD146 as an adverse prognostic factor in uterine sarcoma","volume":"20","author":"Zhou","year":"2015","journal-title":"Eur J Med Res"},{"key":"2020080709363652100_ref22","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1007\/s12094-013-1057-6","article-title":"MCAM expression is associated with poor prognosis in non-small cell lung cancer","volume":"16","author":"Zhang","year":"2014","journal-title":"Clin Transl Oncol"},{"issue":"2","key":"2020080709363652100_ref23","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1155\/2003\/574829","article-title":"Expression of the cell adhesion molecule CD146\/MCAM in non-small cell lung cancer","volume":"25","author":"Kristiansen","year":"2003","journal-title":"Anal Cell Pathol"},{"issue":"11","key":"2020080709363652100_ref24","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1002\/mc.22409","article-title":"CD146 attenuation in cancer-associated fibroblasts promotes pancreatic cancer progression","volume":"55","author":"Zheng","year":"2016","journal-title":"Mol Carcinog"},{"issue":"8","key":"2020080709363652100_ref25","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.1002\/ijc.22082","article-title":"M-CAM expression as marker of poor prognosis in epithelial ovarian cancer","volume":"119","author":"Aldovini","year":"2006","journal-title":"Int J Cancer"},{"key":"2020080709363652100_ref26","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.canlet.2018.05.016","article-title":"CD146 mediates an E-cadherin-to-N-cadherin switch during TGF-\u03b2 signaling-induced epithelial-mesenchymal transition","volume":"430","author":"Ma","year":"2018","journal-title":"Cancer Lett"},{"key":"2020080709363652100_ref27","doi-asserted-by":"crossref","first-page":"4223","DOI":"10.1038\/s41598-017-01061-3","article-title":"Prognostic value of CD146 in solid tumor: A Systematic Review and Meta-analysis","volume":"7","author":"Zeng","year":"2017","journal-title":"Sci Rep"},{"issue":"6B","key":"2020080709363652100_ref28","first-page":"4219","article-title":"A novel antibody AA98 V(H)\/L directed against CD146 efficiently inhibits angiogenesis","volume":"27","author":"Lin","year":"2007","journal-title":"Anticancer Res"},{"issue":"68","key":"2020080709363652100_ref29","doi-asserted-by":"crossref","first-page":"112283","DOI":"10.18632\/oncotarget.22736","article-title":"A novel anti-CD146 antibody specifically targets cancer cells by internalizing the molecule","volume":"8","author":"Nollet","year":"2017","journal-title":"Oncotarget"},{"issue":"26","key":"2020080709363652100_ref30","doi-asserted-by":"crossref","first-page":"40704","DOI":"10.18632\/oncotarget.9930","article-title":"Reduced CD146 expression promotes tumorigenesis and cancer stemness in colorectal cancer through activating Wnt\/\u03b2-catenin signaling","volume":"7","author":"Liu","year":"2016","journal-title":"Oncotarget"},{"issue":"8","key":"2020080709363652100_ref31","doi-asserted-by":"crossref","first-page":"2314","DOI":"10.1158\/0008-5472.CAN-15-1364","article-title":"MCAM and LAMA4 are highly enriched in tumor blood vessels of renal cell carcinoma and predict patient outcome","volume":"76","author":"Wragg","year":"2016","journal-title":"Cancer Res"}],"container-title":["Briefings in Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/bib\/article-pdf\/21\/2\/709\/33583119\/bbz019.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/bib\/article-pdf\/21\/2\/709\/33583119\/bbz019.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,8,7]],"date-time":"2020-08-07T13:51:32Z","timestamp":1596808292000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bib\/article\/21\/2\/709\/5352810"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,28]]},"references-count":31,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2019,2,28]]},"published-print":{"date-parts":[[2020,3,23]]}},"URL":"https:\/\/doi.org\/10.1093\/bib\/bbz019","relation":{},"ISSN":["1467-5463","1477-4054"],"issn-type":[{"type":"print","value":"1467-5463"},{"type":"electronic","value":"1477-4054"}],"subject":[],"published-other":{"date-parts":[[2020,3]]},"published":{"date-parts":[[2019,2,28]]}}}