胃癌相关癌睾抗原筛选与免疫浸润分析

doi:10.11904/j.issn.1002-3070.2022.06.002

摘要/Abstract

摘要： 目的本研究拟在胃癌肿瘤组织和癌旁正常组织差异表达基因中筛选具有免疫功能的癌睾抗原并探讨该类抗原对胃癌生存预后的影响。方法通过TCGA数据库筛选胃癌肿瘤组织和癌旁正常组织差异表达的基因。同时在CTdatabase数据库中筛选已有文献证实的能够诱导免疫反应的癌睾抗原。再从差异表达基因中筛选出具有诱导免疫反应功能的癌睾抗原,并结合患者临床信息进行生存分析,将预后相关癌睾抗原进一步利用CIBERSORT进行免疫浸润分析。结果通过TCGA数据库,共筛选出5 514个差异表达基因。CTdatabase中具有诱导免疫反应功能的癌睾抗原有94个,将其与胃癌差异表达基因进行比对,共得到33个具有诱导免疫反应功能的差异表达癌睾抗原。其中27种癌睾抗原在胃癌肿瘤组织中高表达,分别为ARMC3、CDCA1、CEP55、CSAG2、CT45A1、CTAG2、CTCFL、CXorf61(KK-LC-1)、DDX53、IGF2BP3、MAGEA1、MAGEA10、MAGEA12、MAGEA3、MAGEA4、MAGEA6、MAGEC1、MAGEC2、KIF2C、MPHOSPH1、PLAC1、PRAME、SAGE1、SEMG1、SPAG17、SSX1、TTK,且在文献中被证实具有诱导免疫反应的能力。而肿瘤组织中BAGE2、CCDC110、SPAG4、SPAG8、IGSF11、MAGEB2表达低于正常组织。进一步生存分析发现CEP55、MAGEA10、MAGEA12、MAGEA3、MAGEC1、PLAC1高表达与胃癌患者的较短生存显著相关且与肿瘤免疫微环境中具有抗肿瘤能力的M1型巨噬细胞浸润比例呈正相关。多因素Cox回归分析结果提示CEP55与患者较短生存显著相关。结论本研究从胃癌肿瘤组织高表达的基因中筛选出具有诱导免疫反应功能的癌睾抗原,为胃癌免疫治疗靶点的寻找提供依据。

关键词: 胃癌, 癌睾抗原, 差异表达基因, TCGA, 免疫治疗

Abstract: Objective This study aimed to screen for cancer-testis antigens with immune function in differentially expressed genes between gastric cancer tissues and normal tissues, and to explore the effect of such antigens on survival and prognosis of gastric cancer.Methods The TCGA database was used to screen the genes with significant differences in the expression between gastric cancer tumor tissues and normal tissues.At the same time, the cancer-testis antigens that had been confirmed in the literature and induced immune responses were screened in the CTdatabase.The cancer-testis antigens with the function of inducing immune response were screened from the differentially expressed genes, and the survival analysis was carried out in combination with the clinical information of patients, and the prognosis-related cancer-testis antigens were further analyzed by CIBERSORT for immune infiltration.Results A total of 5514 differentially expressed genes were screened out through the TCGA database.There were 94 cancer-testis antigens with the function of inducing immune response in the CTdatabase.Comparing with the differential expressed genes of gastric cancer, a total of 33 differentially expressed cancer-testis antigens with the function of inducing immune response were obtained.Among them, 27 cancer-testis antigens were highly expressed in gastric cancer tumor tissues, including ARMC3, CDCA1, CEP55, CSAG2, CT45A1, CTAG2, CTCFL, CXorf61(KK-LC-1), DDX53, IGF2BP3, MAGEA1, MAGEA10, MAGEA12, MAGEA3, MAGEA4, MAGEA6, MAGEC1, MAGEC2, KIF2C, MPHOSPH1, PLAC1, PRAME, SAGE1, SEMG1, SPAG17, SSX1, TTK, and had been confirmed in the literature to have the ability to induce immune responses.The expressions of BAGE2, CCDC110, SPAG4, SPAG8, IGSF11 and MAGEB2 in tumor tissues were lower than those in normal tissues.Furthermore, the survival analysis found that the high expressions of CEP55, MAGEA10, MAGEA12, MAGEA3, MAGEC1, and PLAC1 was significantly associated with the shorter survival of patients with gastric cancer, and was positively correlated with the infiltration ratio of M1 macrophages with anti-tumor ability in the tumor immune microenvironment.The multivariate analysis by the Cox regression model showed that the expression of CEP55 was significantly associated with shorter survival of patients.Conclusion In this study, the cancer-testis antigens with the function of inducing immune response were screened from the highly expressed genes in gastric cancer tissues, which provided a basis for the search targets of gastric cancer immunotherapy.

Key words: Gastric cancer, Cancer testis antigen, Differently expressed genes, TCGA, Immunotherapy

中图分类号:

R735.2

杨菊, 刘芹, 刘宝瑞, 魏嘉. 胃癌相关癌睾抗原筛选与免疫浸润分析[J]. 实用肿瘤学杂志, 2022, 36(6): 495-501.

YANG Ju, LIU Qin, LIU Baorui, WEI Jia. Gastric cancer-associated cancer-testis antigen screening and immune infiltration analysis[J]. Journal of Practical Oncology, 2022, 36(6): 495-501.

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链接本文: http://journal09.magtechjournal.com/Jwk3_syzlxzz/CN/10.11904/j.issn.1002-3070.2022.06.002

http://journal09.magtechjournal.com/Jwk3_syzlxzz/CN/Y2022/V36/I6/495

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