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乳腺癌中MAGE-A4表达的评估及其对预后的影响。

Evaluation of MAGE-A4 expression in breast cancer and its impact on prognosis.

作者信息

Nakamura Kaho, Saito Kanako, Higashi Chihiro, Kozuka Yuji, Yuasa Hiroto, Nishimura Yurina, Ishitobi Makoto, Ishihara Mikiya, Mizuno Toshiro, Tawara Isao, Shiraishi Taizo, Ogawa Tomoko, Kageyama Shinichi, Miyahara Yoshihiro

机构信息

Department of Breast Surgery, Mie University Graduate School of Medicine, Tsu, Japan.

Department of Medical Oncology, Mie University Hospital, Tsu, Japan.

出版信息

Cancer Sci. 2025 Mar;116(3):744-752. doi: 10.1111/cas.16433. Epub 2024 Dec 20.

DOI:10.1111/cas.16433
PMID:39704015
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11875791/
Abstract

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.

摘要

黑色素瘤相关抗原（MAGE）-A4是一种癌睾丸抗原，是难治性实体瘤（包括乳腺癌（BC））嵌合抗原受体T细胞疗法的一个有前景的靶点。然而，缺乏针对MAGE-A4的高度特异性抗体是开发针对MAGE-A4的免疫疗法的一个主要挑战。本研究旨在验证一种新型MAGE-A4抗体（E701U）的特异性，并检测其在临床BC样本中的表达情况。将MAGE-A1、-A2B、-A3、-A4、-A6、-A9、-A10和-A12基因转染到HEK293细胞中。使用E701U抗体评估每个插入细胞块中MAGE-A4的表达。随后，我们通过免疫组织化学使用E701U评估了403例原发性BC组织样本中MAGE-A4的表达，并分析了MAGE-A4对早期BC患者的临床影响。结果显示，MAGE-A4的表达仅限于用MAGE-A4基因转导的细胞。在5.7%的BC样本中观察到MAGE-A4表达。三阴性BC中的阳性率显著高于其他亚型。MAGE-A4（+）患者的5年总生存率显著低于MAGE-A4（-）BC患者。此外，MAGE-A4（+）BC患者的5年无复发生存率（RFS）显著低于MAGE-A4（-）BC患者。MAGE-A4表达是RFS的独立预后因素。总之，E701U抗体对MAGE家族基因中的MAGE-A4表达显示出可靠的特异性。MAGE-A4（+）BC患者预后不良，是MAGE-A4特异性免疫疗法的潜在候选者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39d1/11875791/a1c51397a0e2/CAS-116-744-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39d1/11875791/33662deff6d5/CAS-116-744-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39d1/11875791/be82d5c4b1cd/CAS-116-744-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39d1/11875791/3e09739e1b65/CAS-116-744-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39d1/11875791/80664cbef866/CAS-116-744-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39d1/11875791/a42d5c227f4f/CAS-116-744-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39d1/11875791/a1c51397a0e2/CAS-116-744-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39d1/11875791/33662deff6d5/CAS-116-744-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39d1/11875791/be82d5c4b1cd/CAS-116-744-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39d1/11875791/3e09739e1b65/CAS-116-744-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39d1/11875791/80664cbef866/CAS-116-744-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39d1/11875791/a42d5c227f4f/CAS-116-744-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39d1/11875791/a1c51397a0e2/CAS-116-744-g002.jpg

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