Li Xisheng, Ning Lidong, Zhang Qingmei, Ge Yingying, Liu Chang, Bi Shuiqing, Zeng Xia, Nong Weixia, Wu Song, Guo Gaoshui, Xiao Shaowen, Luo Bin, Xie Xiaoxun
Department of Neurosurgery, The People's Hospital of Guangxi Zhuang Autonomous Region China.
Laboratory of Multidisciplinary Treatment and Clinical Translation of Central Nervous System Tumors, The People's Hospital of Guangxi Zhuang Autonomous Region China.
Am J Transl Res. 2020 Dec 15;12(12):7782-7796. eCollection 2020.
Cancer/testis antigens (CTAs) are attractive therapeutic targets for tumor immunotherapy due to their restrictive expression in normal testis but excessive in majority of tumor types. ACTL8, CTCFL, OIP5 and XAGE3 are members of the CTAs family. Currently, the data of ACTL8, CTCFL, OIP5 and XAGE3 expression in glioma is limited. ACTL8, CTCFL, OIP5 and XAGE3 mRAN and protein expressions were detected in 108 glioma samples by Reverse Transcriptase-PCR (RT-PCR) and immunohistochemistry and the correlations between their expressions and clinical indexes were analyzed. Furthermore, their clinical significance on glioma prognosis was determined by follow-up data. The mRNA positive rate of ACTL8, CTCFL, OIP5 and XAGE3 was 15.74% (17/108), 22.22% (24/108), 13.89% (15/108) and 37.96% (41/108), respectively. At least one CTA mRNA was expressed by 61.11% of glioma tissues, while 2 or more by 29.63%. For protein expression, the positive rate of them was 21.30% (23/108), 34.26% (37/108), 19.44% (21/108) and 23.15% (25/108), respectively. At least one CTA protein was expressed by 58.33% of glioma tissues and 2 or more by 29.63%. Although there were no correlations between their mRNA expressions and clinicopathological parameters, the protein expression of ACTL8, OIP5 and XAGE3 was positively correlated with KPS; while the ACTL8 protein was correlated with gender, and OIP5 protein with gender and WHO grade. Kaplan-Meier analysis revealed a significant negative correlation between the CTCFL protein expression, combined ACTL8 and/or CTCFL protein expression and survival. The results suggest that the cohort of glioma does express ACTL8, CTCFL, OIP5 and XAGE3 at both mRNA and protein levels indicating glioma is CTAs-rich tumors. CTCFL protein and the combined ACTL8 and/or CTCFL protein might act as poor prognostic markers for glioma and as potential ideal combined antigens for glioma immunotherapy.
癌胚抗原(CTAs)是肿瘤免疫治疗中颇具吸引力的治疗靶点,因为它们在正常睾丸中表达受限,但在大多数肿瘤类型中表达过度。ACTL8、CTCFL、OIP5和XAGE3是CTAs家族的成员。目前,关于ACTL8、CTCFL、OIP5和XAGE3在胶质瘤中表达的数据有限。通过逆转录聚合酶链反应(RT-PCR)和免疫组织化学检测了108例胶质瘤样本中ACTL8、CTCFL、OIP5和XAGE3的mRNA和蛋白表达,并分析了它们的表达与临床指标之间的相关性。此外,通过随访数据确定了它们对胶质瘤预后的临床意义。ACTL8、CTCFL、OIP5和XAGE3的mRNA阳性率分别为15.74%(17/108)、22.22%(24/108)、13.89%(15/108)和37.96%(41/108)。61.11%的胶质瘤组织至少表达一种CTA mRNA,29.63%的组织表达两种或更多种。蛋白表达方面,它们的阳性率分别为21.30%(23/108)、34.26%(37/108)、19.44%(21/108)和23.15%(25/108)。58.33%的胶质瘤组织至少表达一种CTA蛋白,29.63%的组织表达两种或更多种。虽然它们的mRNA表达与临床病理参数之间无相关性,但ACTL8、OIP5和XAGE3的蛋白表达与KPS呈正相关;而ACTL8蛋白与性别相关,OIP5蛋白与性别和世界卫生组织(WHO)分级相关。Kaplan-Meier分析显示,CTCFL蛋白表达、联合ACTL8和/或CTCFL蛋白表达与生存率之间存在显著负相关。结果表明,胶质瘤群体在mRNA和蛋白水平上均表达ACTL8、CTCFL、OIP5和XAGE3,表明胶质瘤是富含CTAs的肿瘤。CTCFL蛋白以及联合ACTL8和/或CTCFL蛋白可能是胶质瘤预后不良的标志物,也是胶质瘤免疫治疗潜在的理想联合抗原。