结肠直肠癌B7S1表达与免疫浸润的关系

Expression of B7S1 related with immune infiltration in colorectal cancer

目的:探讨B7S1(由VTCN1编码)mRNA水平及蛋白质水平在结肠直肠癌(colorectal cancer,CRC)中的表达,分析其与临床病理特征、免疫细胞浸润以及预后的相关性,评估其作为CRC免疫治疗靶点的潜在应用价值。方法:利用Oncomine及TIMER数据库检索VTCN1在人体多种实体瘤中的表达。利用UALCAN及LinkedOmics数据库分析VTCN1表达量与CRC临床病理特征的关系。利用人类蛋白质图谱、Kaplan-Meier Plotter和TIMER数据库分析评估CRC中VTCN1表达量与免疫细胞浸润及临床预后的相关性。收集瑞金医院(北部院区)24例CRC病人,利用免疫荧光染色技术检测B7S1蛋白水平在CRC和正常肠道组织中的表达。结果:通过数据库发现VTCN1在人体多种实体肿瘤中表达。与正常肠道组织对比,VTCN1在CRC的多种亚型中均高表达。上调表达的VTCN1与肿瘤分期、淋巴结转移、远处转移、错配修复状态及总生存率相关。VTCN1与免疫细胞浸润存在一定的相关性。免疫荧光染色结果显示,相较于正常肠道组织,B7S1蛋白水平在CRC中上调表达。在CD45^(-)细胞及CD45^(+)免疫细胞中均有表达。结论:B7S1作为共抑制性免疫检查点分子,可能成为CRC潜在的预后因子或免疫治疗靶点。

Objective To investigate the expression of B7 S1 mRNA which is encoded by VTCN1 and protein levels in colorectal cancer(CRC)with the analysis of relation to clinicopathological characteristics,immune cell infiltration,and prognosis for the evaluation as a immunotherapeutic target in CRC.Methods Both Oncomine and TIMER databases were used to review the expression of VTCN1 in a variety of human solid tumors.The relationship between the expression of VTCN1 and the clinicopathological characteristics of CRC was analyzed using UALCAN and LinkedOmics databases.The expression of VTCN1 which is related with immune infiltration and clinical prognosis was evaluated using Human Protein Atlas database,Kaplan-Meier Plotter and TIMER database.A total of 24 patients with CRC in Ruijin Hospital(North)were collected and the expression of B7 S1 protein in both CRC and normal intestinal tissues was detected by immunoflu-orescence staining.Results It was found in database that VTCN1 was expressed in many human solid tumors.VTCN1 was highly expressed in various subtypes of CRC when compared with that in normal intestinal tissues.The up-regulated VTCN1 was related to tumor stage,lymph node metastasis,distant metastasis,mismatch repair and overall survival rate.VTCN1 was also related to the immune cell infiltration.Immunofluorescence analysis showed that the protein of B7 S1 was up-regulated in CRC when compared with that in normal intestinal tissues,and it was expressed in CD45^(-) cells and CD45^(+)cells.Conclusions As co-inhibitory immune checkpoint molecule,B7 S1 may be a potential prognostic factor and might become the target of immunotherapy for CRC.