结直肠癌组织免疫细胞中VISTA和PD-L1表达及其与预后关联

Expression of VISTA and PD-L1 in the immune cells of the patients with colorectal cancer and its correlation with prognosis

目的探讨VISTA和程序性细胞死亡配体1(PD-L1)在结直肠癌肿瘤细胞和免疫细胞中表达情况及其临床意义。方法选取武汉大学中南医院2005-07-01-2013-07-01归档的62例结直肠癌患者标本及相应癌旁组织(>5 cm)进行研究,采用免疫组化法检测VISTA和PD-L1蛋白表达情况及相关性,评估其与患者临床病理特征和总体生存率关系。采用Kaplan-Meier法和Log-rank检验进行生存分析,并利用Cox比例风险模型进行单因素和多因素分析对生存有影响的指标。结果与癌旁组织相比,VISTA和PD-L1在结直肠癌肿瘤组织中过表达,阳性表达率分别为24.2%和16.1%。结直肠癌肿瘤细胞中VISTA表达(χ^(2)=7.886,P=0.010)和PD-L1表达(χ^(2)=10.962,P=0.004)与TNM分期有统计学意义的关联;免疫细胞中PD-L1表达与年龄有统计学意义的关联,χ^(2)=12.579,P=0.001。免疫细胞中VISTA和PD-L1主要在淋巴细胞和巨噬细胞中高表达,分别为58.1%和27.4%,二者与结直肠癌患者良好生存率均有统计学意义的关联(P=0.018,P=0.030);而PD-L1在肿瘤细胞中过表达预示结直肠癌患生存期较差(P=0.025)。结直肠癌组织免疫细胞中VISTA和PD-L1表达呈低度正相关,r_(s)=0.322,P=0.008;肿瘤细胞中VISTA和PD-L1表达呈低度正相关,r_(s)=0.310,P=0.014。Cox多因素分析结果显示,免疫细胞中VISTA(HR=0.451,95%CI为0.211~0.964,P=0.040)和PD-L1(HR=0.253,95%CI为0.080~0.806,P=0.020)、肿瘤细胞中PD-L1(HR=4.970,95%CI为1.819~13.574,P=0.002)、淋巴结转移(HR=2.912,95%CI为1.366~6.207,P=0.006)是结直肠癌患者总生存期的独立预后指标。结论VISTA和PD-L1在免疫细胞中高表达与结直肠癌的良好预后有统计学意义的关联,并可作为结直肠癌的一个独立预后因素。

Objective To investigate the expression patterns and their clinical significance of VISTA and PD-L1in the tumor cells and immune cells of CRC.Methods A total of 62CRC cases and the corresponding noncancerous tissues(far from>5cm of cancer)were collected from Department of Pathology,Zhongnan Hospital of Wuhan University from July1,2005to July 1,2013.Immunohistochemistry was performed to examine the expression of VISTA and PD-L1proteins.We measured expression patterns and location of these targets,evaluating their association with clinicopathological features and overall survival.Results Compared with noncancerous tissues,VISTA and PD-L1were significantly overexpressed in the tumor cells of colorectal cancer,whose positive rates were 24.2%and 16.1%,respectively.In colorectal cancer patients,VISTA and PD-L1expression in tumor cells demonstrated a statistically significant correlation with TNM stage(χ^(2)=7.886,P=0.005;χ^(2)=10.962,P=0.004).In colorectal cancer cohort,high VISTA and PD-L1expression in the immune cells(ICs)including lymphocytes and macrophages were 58.1%(36/62)and 27.4%(17/62),respectively.They were statistically significant associated with a favorable survival(P=0.018,P=0.030),while PD-L1overexpression in TCs indicated a worse survival(P=0.025).There was a low degree of positive correlation between the expression of VISTA and PD-L1in immune cells and tumor cells of CRC tissues(r_(s)=0.322,P=0.008;r_(s)=0.310,P=0.014).COX multivariate analysis results showed that VISTA (HR=0.451,95%CI:0.211-0.964,P=0.040)and PD-L1(HR=0.253,95%CI:0.080-0.806,P=0.020)in immune cells,PD-L1in tumor cells(HR=4.970,95%CI:1.819-13.574,P=0.002),lymph node metastasis(HR=2.912,95%CI:1.366-6.207,P=0.006)were independent prognostic indicators of the overall survival of colorectal cancer patients.Conclusion High expression of VISTA and PD-L1in ICs are significantly associated with favorable prognosis,and they survival of colorectal cancer patients could be regarded as an independent prognostic predictor of CRC.