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新型癌胚抗原TMEM31在转移性黑色素瘤进展过程中的表达增加。

Expression of novel cancer/testis antigen TMEM31 increases during metastatic melanoma progression.

作者信息

Li Jiaqiang, Zou Xiaowen, Li Cailing, Zhong Jianhua, Chen Yan, Zhang Xiaoyue, Qi Fuming, Li Mengshuo, Cai Zhiming, Tang Aifa

机构信息

Department of Pediatric Urology, Shenzhen Children's Hospital, Shenzhen, Guangdong 518026, P.R. China.

Shantou University Medical College, Shantou, Guangdong 515063, P.R. China.

出版信息

Oncol Lett. 2017 Apr;13(4):2269-2273. doi: 10.3892/ol.2017.5728. Epub 2017 Feb 13.

Abstract

Cancer/testis (CT) antigens are promising targets for immunotherapy due to their restricted expression in the germ cells of the testis in healthy tissue and high immunogenicity. The aim of the present study was to determine whether transmembrane protein 31 (TMEM31) is a CT antigen and to investigate the pattern of TMEM31 expression during the progression of melanoma. The pattern of expression of human TMEM31 mRNA in multiple human tissues was determined through reverse transcription-polymerase chain reaction analysis. TMEM31 protein expression was analyzed in the human testis, in addition to 128 primary melanoma and 64 metastatic melanoma samples through immunohistochemistry analysis. TMEM31 was identified to be predominantly expressed in the testis and weakly expressed in the placenta. In addition, TMEM31 protein expression was detected in 120/190 (63.16%) melanoma samples (primary and metastatic). The intensity of TMEM31 staining in metastatic and primary melanomas was determined through semiquantitative integrated optical density (IOD) analysis, and identified to be significantly increased in metastatic melanoma compared with primary melanoma (0.24±0.03 vs. 0.09±0.01 IOD/area; P<0.001). The expression of TMEM31 protein was significantly increased in metastatic compared with primary melanoma samples (76.56 vs. 56.35%; P=0.017). The results of the present study suggest that TMEM31 is a novel CT antigen that serves an essential role in melanoma metastasis, in addition to being a potential immunotherapeutic target for the treatment of patients with melanoma.

摘要

癌胚/睾丸(CT)抗原因其在健康组织睾丸生殖细胞中的限制性表达和高免疫原性,成为免疫治疗的有前景靶点。本研究旨在确定跨膜蛋白31(TMEM31)是否为CT抗原,并研究其在黑色素瘤进展过程中的表达模式。通过逆转录-聚合酶链反应分析确定人TMEM31 mRNA在多种人体组织中的表达模式。除了通过免疫组织化学分析128例原发性黑色素瘤和64例转移性黑色素瘤样本外,还对人睾丸中的TMEM31蛋白表达进行了分析。发现TMEM31主要在睾丸中表达,在胎盘中弱表达。此外,在190例黑色素瘤样本(原发性和转移性)中的120例(63.16%)检测到TMEM31蛋白表达。通过半定量积分光密度(IOD)分析确定转移性和原发性黑色素瘤中TMEM31染色强度,发现与原发性黑色素瘤相比,转移性黑色素瘤中TMEM31染色强度显著增加(0.24±0.03 vs. 0.09±0.01 IOD/面积;P<0.001)。与原发性黑色素瘤样本相比,转移性黑色素瘤中TMEM31蛋白表达显著增加(76.56%对56.35%;P=0.017)。本研究结果表明,TMEM31是一种新型CT抗原,除了作为治疗黑色素瘤患者的潜在免疫治疗靶点外,在黑色素瘤转移中也起着重要作用。

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