{"title":"评估乳腺癌中 MAGE-A4 的表达及其对预后的影响。","authors":"Kaho Nakamura, Kanako Saito, Chihiro Higashi, Yuji Kozuka, Hiroto Yuasa, Yurina Nishimura, Makoto Ishitobi, Mikiya Ishihara, Toshiro Mizuno, Isao Tawara, Taizo Shiraishi, Tomoko Ogawa, Shinichi Kageyama, Yoshihiro Miyahara","doi":"10.1111/cas.16433","DOIUrl":null,"url":null,"abstract":"<p><p>Melanoma-associated antigen (MAGE)-A4, a cancer testis antigen, presents a promising target for chimeric antigen receptor T cell therapy in refractory solid tumors, including breast cancer (BC). However, the lack of highly specific Abs against MAGE-A4 is a major challenge for the development of MAGE-A4-targeted immunotherapies. This study aimed to validate the specificity of a novel MAGE-A4 Ab (E701U) and examine MAGE-A4 expression in clinical BC samples. MAGE-A1, -A2B, -A3, -A4, -A6, -A9, -A10, and -A12 genes were transfected into HEK293 cells. MAGE-A4 expression in each inserted cell block was evaluated using an E701U Ab. Subsequently, we evaluated MAGE-A4 expression in 403 primary BC tissue samples by immunohistochemistry using E701U and analyzed the clinical impact of MAGE-A4 in patients with early BC. The results showed that MAGE-A4 expression was limited to cells transduced with the MAGE-A4 gene. MAGE-A4 expression was observed in 5.7% of the BC samples. Positivity in triple-negative BC was significantly higher than in the other subtypes. The 5-year overall survival rate of patients with MAGE-A4(+) was significantly worse than those with MAGE-A4(-) BC. Moreover, the 5-year recurrence-free survival (RFS) rate of patients with MAGE-A4(+) BC was significantly lower than that of patients with MAGE-A4(-) BC. MAGE-A4 expression was an independent prognostic factor for RFS. In conclusion, the E701U Ab showed reliable specificity for MAGE-A4 expression among MAGE family genes. Patients with MAGE-A4(+) BC have an unfavorable prognosis and represent potential candidates for MAGE-A4-specific immunotherapy.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7000,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Evaluation of MAGE-A4 expression in breast cancer and its impact on prognosis.\",\"authors\":\"Kaho Nakamura, Kanako Saito, Chihiro Higashi, Yuji Kozuka, Hiroto Yuasa, Yurina Nishimura, Makoto Ishitobi, Mikiya Ishihara, Toshiro Mizuno, Isao Tawara, Taizo Shiraishi, Tomoko Ogawa, Shinichi Kageyama, Yoshihiro Miyahara\",\"doi\":\"10.1111/cas.16433\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Melanoma-associated antigen (MAGE)-A4, a cancer testis antigen, presents a promising target for chimeric antigen receptor T cell therapy in refractory solid tumors, including breast cancer (BC). However, the lack of highly specific Abs against MAGE-A4 is a major challenge for the development of MAGE-A4-targeted immunotherapies. This study aimed to validate the specificity of a novel MAGE-A4 Ab (E701U) and examine MAGE-A4 expression in clinical BC samples. MAGE-A1, -A2B, -A3, -A4, -A6, -A9, -A10, and -A12 genes were transfected into HEK293 cells. MAGE-A4 expression in each inserted cell block was evaluated using an E701U Ab. Subsequently, we evaluated MAGE-A4 expression in 403 primary BC tissue samples by immunohistochemistry using E701U and analyzed the clinical impact of MAGE-A4 in patients with early BC. The results showed that MAGE-A4 expression was limited to cells transduced with the MAGE-A4 gene. MAGE-A4 expression was observed in 5.7% of the BC samples. Positivity in triple-negative BC was significantly higher than in the other subtypes. The 5-year overall survival rate of patients with MAGE-A4(+) was significantly worse than those with MAGE-A4(-) BC. Moreover, the 5-year recurrence-free survival (RFS) rate of patients with MAGE-A4(+) BC was significantly lower than that of patients with MAGE-A4(-) BC. MAGE-A4 expression was an independent prognostic factor for RFS. In conclusion, the E701U Ab showed reliable specificity for MAGE-A4 expression among MAGE family genes. Patients with MAGE-A4(+) BC have an unfavorable prognosis and represent potential candidates for MAGE-A4-specific immunotherapy.</p>\",\"PeriodicalId\":48943,\"journal\":{\"name\":\"Cancer Science\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":5.7000,\"publicationDate\":\"2024-12-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Science\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/cas.16433\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Science","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/cas.16433","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}
Evaluation of MAGE-A4 expression in breast cancer and its impact on prognosis.
Melanoma-associated antigen (MAGE)-A4, a cancer testis antigen, presents a promising target for chimeric antigen receptor T cell therapy in refractory solid tumors, including breast cancer (BC). However, the lack of highly specific Abs against MAGE-A4 is a major challenge for the development of MAGE-A4-targeted immunotherapies. This study aimed to validate the specificity of a novel MAGE-A4 Ab (E701U) and examine MAGE-A4 expression in clinical BC samples. MAGE-A1, -A2B, -A3, -A4, -A6, -A9, -A10, and -A12 genes were transfected into HEK293 cells. MAGE-A4 expression in each inserted cell block was evaluated using an E701U Ab. Subsequently, we evaluated MAGE-A4 expression in 403 primary BC tissue samples by immunohistochemistry using E701U and analyzed the clinical impact of MAGE-A4 in patients with early BC. The results showed that MAGE-A4 expression was limited to cells transduced with the MAGE-A4 gene. MAGE-A4 expression was observed in 5.7% of the BC samples. Positivity in triple-negative BC was significantly higher than in the other subtypes. The 5-year overall survival rate of patients with MAGE-A4(+) was significantly worse than those with MAGE-A4(-) BC. Moreover, the 5-year recurrence-free survival (RFS) rate of patients with MAGE-A4(+) BC was significantly lower than that of patients with MAGE-A4(-) BC. MAGE-A4 expression was an independent prognostic factor for RFS. In conclusion, the E701U Ab showed reliable specificity for MAGE-A4 expression among MAGE family genes. Patients with MAGE-A4(+) BC have an unfavorable prognosis and represent potential candidates for MAGE-A4-specific immunotherapy.
期刊介绍：
Cancer Science (formerly Japanese Journal of Cancer Research) is a monthly publication of the Japanese Cancer Association. First published in 1907, the Journal continues to publish original articles, editorials, and letters to the editor, describing original research in the fields of basic, translational and clinical cancer research. The Journal also accepts reports and case reports.
Cancer Science aims to present highly significant and timely findings that have a significant clinical impact on oncologists or that may alter the disease concept of a tumor. The Journal will not publish case reports that describe a rare tumor or condition without new findings to be added to previous reports; combination of different tumors without new suggestive findings for oncological research; remarkable effect of already known treatments without suggestive data to explain the exceptional result. Review articles may also be published.
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