{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T03:32:17Z","timestamp":1773804737639,"version":"3.50.1"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2015,7,15]],"date-time":"2015-07-15T00:00:00Z","timestamp":1436918400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2015,7,15]],"date-time":"2015-07-15T00:00:00Z","timestamp":1436918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The cancer testis antigen, melanoma-associated antigen A9 (MAGE-A9), is expressed in many kinds of different human cancers and is an important target for immunotherapy. However, the clinicopathologic significance of MAGE-A9 in epithelial ovarian cancer (EOC) is unknown. In this study, real-time PCR (12 carcinomas of high FIGO stage, 12 carcinomas of low FIGO stage and 20 normal ovary or fallopian tube tissues) and immunohistochemistry by tissue microarrays (128 carcinomas and 112 normal ovary or fallopian tube tissues, benign or borderline ovarian tumor tissues) were performed to characterize expression of MAGE-A9 in EOC. We found that significantly higher MAGE-A9 mRNA expression in EOC tumors than that in normal ovary or fallopian tube tissues (all <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). Protein expression of MAGE-A9 was significantly associated with FIGO stage, high histological grade, level of CA-125 and metastasis. Consistent with the associated poor clinicopathologic features, patients with MAGE-A9<jats:sup>H (high-expressing)<\/jats:sup> tumors had a worse overall survival as compared to patients with MAGE-A9<jats:sup>L (low or none-expressing)<\/jats:sup> tumors. Further studies revealed that MAGE-A9 overexpression was an independent prognostic factor for overall survival (OS). Multivariate analysis showed that patients with MAGE-A9 overexpressing tumors had extremely poor OS. These findings indicate that MAGE-A9 expression may be helpful in predicting EOC prognosis.<\/jats:p>","DOI":"10.1038\/srep12104","type":"journal-article","created":{"date-parts":[[2015,7,15]],"date-time":"2015-07-15T11:16:18Z","timestamp":1436958978000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Overexpression of MAGE-A9 Is Predictive of Poor Prognosis in Epithelial Ovarian Cancer"],"prefix":"10.1038","volume":"5","author":[{"given":"Yunzhao","family":"Xu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenyi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuquan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lizhou","family":"Jia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianfei","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2015,7,15]]},"reference":[{"key":"BFsrep12104_CR1","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.ejogrb.2011.04.023","volume":"158","author":"B Zhang","year":"2011","unstructured":"Zhang, B., Cai, F. F. & Zhong, X. Y. An overview of biomarkers for the ovarian cancer diagnosis. Eur J Obstet Gynecol Reprod Biol 158, 119\u2013123 (2011).","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"BFsrep12104_CR2","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1158\/1078-0432.CCR-09-2642","volume":"16","author":"DC Corney","year":"2010","unstructured":"Corney, D. C. et al. Frequent downregulation of miR-34 family in human ovarian cancers. Clin Cancer Res 16, 1119\u20131128 (2010).","journal-title":"Clin Cancer Res"},{"key":"BFsrep12104_CR3","doi-asserted-by":"publisher","first-page":"634289","DOI":"10.1155\/2014\/634289","volume":"2014","author":"JH Kim","year":"2014","unstructured":"Kim, J. H. et al. Mass spectrometric screening of ovarian cancer with serum glycans. Dis Markers 2014, 634289 (2014).","journal-title":"Dis Markers"},{"key":"BFsrep12104_CR4","doi-asserted-by":"publisher","first-page":"x35","DOI":"10.1093\/annonc\/mdt467","volume":"24","author":"M Markman","year":"2013","unstructured":"Markman, M. Surgical intervention in relapsed ovarian cancer is beneficial: contra. Ann Oncol 24 Suppl 10, x35\u201336 (2013).","journal-title":"Ann Oncol"},{"key":"BFsrep12104_CR5","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1186\/s13073-014-0057-7","volume":"6","author":"J Jeon","year":"2014","unstructured":"Jeon, J. et al. A systematic approach to identify novel cancer drug targets using machine learning, inhibitor design and high-throughput screening. Genome Med 6, 57 (2014).","journal-title":"Genome Med"},{"key":"BFsrep12104_CR6","doi-asserted-by":"publisher","first-page":"5811","DOI":"10.1038\/srep05811","volume":"4","author":"H Zhang","year":"2014","unstructured":"Zhang, H. et al. ROR1 expression correlated with poor clinical outcome in human ovarian cancer. Sci Rep 4, 5811 (2014).","journal-title":"Sci Rep"},{"key":"BFsrep12104_CR7","doi-asserted-by":"publisher","first-page":"1931","DOI":"10.1158\/1535-7163.MCT-10-0239","volume":"9","author":"SK Pal","year":"2010","unstructured":"Pal, S. K., Figlin, R. A. & Reckamp, K. Targeted therapies for non-small cell lung cancer: an evolving landscape. Mol Cancer Ther 9, 1931\u20131944 (2010).","journal-title":"Mol Cancer Ther"},{"key":"BFsrep12104_CR8","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1097\/JTO.0b013e3181758141","volume":"3","author":"K Kelly","year":"2008","unstructured":"Kelly, K. & Huang, C. Biological agents in non-small cell lung cancer: a review of recent advances and clinical results with a focus on epidermal growth factor receptor and vascular endothelial growth factor. J Thorac Oncol 3, 664\u2013673 (2008).","journal-title":"J Thorac Oncol"},{"key":"BFsrep12104_CR9","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1158\/1078-0432.CCR-11-2017","volume":"18","author":"DR Parkinson","year":"2012","unstructured":"Parkinson, D. R., Johnson, B. E. & Sledge, G. W. Making personalized cancer medicine a reality: challenges and opportunities in the development of biomarkers and companion diagnostics. Clin Cancer Res 18, 619\u2013624 (2012).","journal-title":"Clin Cancer Res"},{"key":"BFsrep12104_CR10","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1038\/nrc1669","volume":"5","author":"AJ Simpson","year":"2005","unstructured":"Simpson, A. J., Caballero, O. L., Jungbluth, A., Chen, Y. T. & Old, L. J. Cancer\/testis antigens, gametogenesis and cancer. Nat Rev Cancer 5, 615\u2013625 (2005).","journal-title":"Nat Rev Cancer"},{"key":"BFsrep12104_CR11","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1002\/jnr.10160","volume":"67","author":"PA Barker","year":"2002","unstructured":"Barker, P. A. & Salehi, A. The MAGE proteins: emerging roles in cell cycle progression, apoptosis and neurogenetic disease. J Neurosci Res 67, 705\u2013712 (2002).","journal-title":"J Neurosci Res"},{"key":"BFsrep12104_CR12","doi-asserted-by":"publisher","first-page":"55","DOI":"10.2739\/kurumemedj.43.55","volume":"43","author":"M Sakata","year":"1996","unstructured":"Sakata, M. Expression of MAGE gene family in lung cancers. Kurume Med J 43, 55\u201361 (1996).","journal-title":"Kurume Med J"},{"key":"BFsrep12104_CR13","first-page":"6682","volume":"61","author":"M Otte","year":"2001","unstructured":"Otte, M. et al. MAGE-A gene expression pattern in primary breast cancer. Cancer Res 61, 6682\u20136687 (2001).","journal-title":"Cancer Res"},{"key":"BFsrep12104_CR14","doi-asserted-by":"publisher","first-page":"1809","DOI":"10.1158\/1078-0432.CCR-04-1365","volume":"11","author":"M Li","year":"2005","unstructured":"Li, M. et al. Expression profile of cancer-testis genes in 121 human colorectal cancer tissue and adjacent normal tissue. Clin Cancer Res 11, 1809\u20131814 (2005).","journal-title":"Clin Cancer Res"},{"key":"BFsrep12104_CR15","first-page":"171","volume":"31","author":"N Yanagawa","year":"2011","unstructured":"Yanagawa, N., Tamura, G., Oizumi, H., Endoh, M. & Motoyama, T. MAGE expressions mediated by demethylation of MAGE promoters induce progression of non-small cell lung cancer. Anticancer Res 31, 171\u2013175 (2011).","journal-title":"Anticancer Res"},{"key":"BFsrep12104_CR16","doi-asserted-by":"publisher","first-page":"2269","DOI":"10.1002\/ijc.21656","volume":"118","author":"J Kim","year":"2006","unstructured":"Kim, J. et al. The clinical significance of MAGEA3 expression in pancreatic cancer. Int J Cancer 118, 2269\u20132275 (2006).","journal-title":"Int J Cancer"},{"key":"BFsrep12104_CR17","first-page":"1843","volume":"27","author":"CM Pereira","year":"2012","unstructured":"Pereira, C. M. et al. Evaluation of MAGE A1 in oral squamous cell carcinoma. Oncol Rep 27, 1843\u20131848 (2012).","journal-title":"Oncol Rep"},{"key":"BFsrep12104_CR18","first-page":"5544","volume":"61","author":"P Chomez","year":"2001","unstructured":"Chomez, P. et al. An overview of the MAGE gene family with the identification of all human members of the family. Cancer Res 61, 5544\u20135551 (2001).","journal-title":"Cancer Res"},{"key":"BFsrep12104_CR19","doi-asserted-by":"publisher","first-page":"1914","DOI":"10.1073\/pnas.94.5.1914","volume":"94","author":"YT Chen","year":"1997","unstructured":"Chen, Y. T. et al. A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening. Proc Natl Acad Sci USA 94, 1914\u20131918 (1997).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep12104_CR20","doi-asserted-by":"publisher","first-page":"8104","DOI":"10.1158\/0008-5472.CAN-08-2132","volume":"68","author":"W Liu","year":"2008","unstructured":"Liu, W., Cheng, S., Asa, S. L. & Ezzat, S. The melanoma-associated antigen A3 mediates fibronectin-controlled cancer progression and metastasis. Cancer Res 68, 8104\u20138112 (2008).","journal-title":"Cancer Res"},{"key":"BFsrep12104_CR21","doi-asserted-by":"publisher","first-page":"8055","DOI":"10.1158\/1078-0432.CCR-05-1203","volume":"11","author":"AO Gure","year":"2005","unstructured":"Gure, A. O. et al. Cancer-testis genes are coordinately expressed and are markers of poor outcome in non-small cell lung cancer. Clin Cancer Res 11, 8055\u20138062 (2005).","journal-title":"Clin Cancer Res"},{"key":"BFsrep12104_CR22","doi-asserted-by":"publisher","first-page":"2396","DOI":"10.1200\/JCO.2012.43.7103","volume":"31","author":"J Vansteenkiste","year":"2013","unstructured":"Vansteenkiste, J. et al. Adjuvant MAGE-A3 immunotherapy in resected non-small-cell lung cancer: phase II randomized study results. J Clin Oncol 31, 2396\u20132403 (2013).","journal-title":"J Clin Oncol"},{"key":"BFsrep12104_CR23","doi-asserted-by":"publisher","first-page":"2413","DOI":"10.1200\/JCO.2012.43.7111","volume":"31","author":"WH Kruit","year":"2013","unstructured":"Kruit, W. H. et al. Selection of immunostimulant AS15 for active immunization with MAGE-A3 protein: results of a randomized phase II study of the European Organisation for Research and Treatment of Cancer Melanoma Group in Metastatic Melanoma. J Clin Oncol 31, 2413\u20132420 (2013).","journal-title":"J Clin Oncol"},{"key":"BFsrep12104_CR24","doi-asserted-by":"crossref","first-page":"12398","DOI":"10.18632\/oncotarget.2643","volume":"5","author":"R Sun","year":"2014","unstructured":"Sun, R. et al. Prognostic value of LAMP3 and TP53 overexpression in benign and malignant gastrointestinal tissues. Oncotarget 5, 12398\u201312409 (2014).","journal-title":"Oncotarget"},{"key":"BFsrep12104_CR25","doi-asserted-by":"publisher","first-page":"7252","DOI":"10.1158\/1078-0432.CCR-04-0713","volume":"10","author":"RL Camp","year":"2004","unstructured":"Camp, R. L., Dolled-Filhart, M. & Rimm, D. L. X-tile: a new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization. Clin Cancer Res 10, 7252\u20137259 (2004).","journal-title":"Clin Cancer Res"},{"key":"BFsrep12104_CR26","doi-asserted-by":"publisher","first-page":"e104099","DOI":"10.1371\/journal.pone.0104099","volume":"9","author":"S Daudi","year":"2014","unstructured":"Daudi, S. et al. Expression and immune responses to MAGE antigens predict survival in epithelial ovarian cancer. PLoS One 9, e104099 (2014).","journal-title":"PLoS One"},{"key":"BFsrep12104_CR27","doi-asserted-by":"publisher","first-page":"2170","DOI":"10.1002\/ijc.22282","volume":"120","author":"V Picard","year":"2007","unstructured":"Picard, V., Bergeron, A., Larue, H. & Fradet, Y. MAGE-A9 mRNA and protein expression in bladder cancer. Int J Cancer 120, 2170\u20132177 (2007).","journal-title":"Int J Cancer"},{"key":"BFsrep12104_CR28","doi-asserted-by":"publisher","first-page":"1365","DOI":"10.1002\/ijc.24503","volume":"125","author":"A Bergeron","year":"2009","unstructured":"Bergeron, A. et al. High frequency of MAGE-A4 and MAGE-A9 expression in high-risk bladder cancer. Int J Cancer 125, 1365\u20131371 (2009).","journal-title":"Int J Cancer"},{"key":"BFsrep12104_CR29","doi-asserted-by":"publisher","first-page":"311","DOI":"10.3109\/00365599.2012.740070","volume":"47","author":"G Hatiboglu","year":"2013","unstructured":"Hatiboglu, G. et al. Prognostic value of melanoma-associated antigen A9 in renal cell carcinoma. Scand J Urol 47, 311\u2013322 (2013).","journal-title":"Scand J Urol"},{"key":"BFsrep12104_CR30","doi-asserted-by":"publisher","first-page":"6625","DOI":"10.1038\/srep06625","volume":"4","author":"X Gu","year":"2014","unstructured":"Gu, X. et al. High expression of MAGE-A9 correlates with unfavorable survival in hepatocellular carcinoma. Sci Rep 4, 6625 (2014).","journal-title":"Sci Rep"},{"key":"BFsrep12104_CR31","first-page":"6734","volume":"7","author":"L Han","year":"2014","unstructured":"Han, L., Jiang, B., Wu, H., Zhang, S. & Lu, X. Expression and prognostic value of MAGE-A9 in laryngeal squamous cell carcinoma. Int J Clin Exp Pathol 7, 6734\u20136742 (2014).","journal-title":"Int J Clin Exp Pathol"},{"key":"BFsrep12104_CR32","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1016\/j.yexmp.2014.11.001","volume":"97","author":"X Xu","year":"2014","unstructured":"Xu, X. et al. Overexpression of MAGE-A9 predicts unfavorable outcome in breast cancer. Exp Mol Pathol 97, 579\u2013584 (2014).","journal-title":"Exp Mol Pathol"},{"key":"BFsrep12104_CR33","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1002\/ijc.10967","volume":"104","author":"S Eichmuller","year":"2003","unstructured":"Eichmuller, S., Usener, D., Thiel, D. & Schadendorf, D. Tumor-specific antigens in cutaneous T-cell lymphoma: expression and sero-reactivity. Int J Cancer 104, 482\u2013487 (2003).","journal-title":"Int J Cancer"},{"key":"BFsrep12104_CR34","doi-asserted-by":"publisher","first-page":"1662","DOI":"10.3324\/haematol.2010.037978","volume":"96","author":"M van Duin","year":"2011","unstructured":"van Duin, M. et al. Cancer testis antigens in newly diagnosed and relapse multiple myeloma: prognostic markers and potential targets for immunotherapy. Haematologica 96, 1662\u20131669 (2011).","journal-title":"Haematologica"},{"key":"BFsrep12104_CR35","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.arcmed.2013.10.005","volume":"45","author":"SY Hou","year":"2014","unstructured":"Hou, S. Y. et al. Expressions of MAGE-A9 and MAGE-A11 in breast cancer and their expression mechanism. Arch Med Res 45, 44\u201351 (2014).","journal-title":"Arch Med Res"},{"key":"BFsrep12104_CR36","doi-asserted-by":"publisher","first-page":"15505","DOI":"10.1074\/jbc.M310437200","volume":"279","author":"T Sakurai","year":"2004","unstructured":"Sakurai, T. et al. A cleaved form of MAGE-A4 binds to Miz-1 and induces apoptosis in human cells. J Biol Chem 279, 15505\u201315514 (2004).","journal-title":"J Biol Chem"},{"key":"BFsrep12104_CR37","first-page":"2778","volume":"9","author":"Z Duan","year":"2003","unstructured":"Duan, Z. et al. Overexpression of MAGE\/GAGE genes in paclitaxel\/doxorubicin-resistant human cancer cell lines. Clin Cancer Res 9, 2778\u20132785 (2003).","journal-title":"Clin Cancer Res"},{"key":"BFsrep12104_CR38","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1007\/s00408-009-9181-3","volume":"187","author":"SH Kim","year":"2009","unstructured":"Kim, S. H. et al. Expression of cancer-testis antigens MAGE-A3\/6 and NY-ESO-1 in non-small-cell lung carcinomas and their relationship with immune cell infiltration. Lung 187, 401\u2013411 (2009).","journal-title":"Lung"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep12104","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep12104.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep12104.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T13:55:27Z","timestamp":1672926927000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep12104"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,7,15]]},"references-count":38,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2015,12,18]]}},"alternative-id":["BFsrep12104"],"URL":"https:\/\/doi.org\/10.1038\/srep12104","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,7,15]]},"assertion":[{"value":"19 November 2014","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 June 2015","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 July 2015","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"12104"}}