肿瘤浸润淋巴细胞相关因子和PD-L1在dMMR结直肠癌中的表达及临床意义  

Expression and clinical significance of tumor infiltrating lymphocyte-related factors and PD-L1 in dMMR colorectal cancer

作　　者：张飞[1] 王雅婧 李合 步鹏[2] 白中元 张伟[3] 郗彦凤[2] Zhang Fei;Wang Yajing;Li He;Bu Peng;Bai Zhongyuan;Zhang Wei;Xi Yanfeng(School of Basic Medicine,Shanxi Medical University,Taiyuan 030000,China;Department of Pathology,Shanxi Provincial Cancer Hospital,Taiyuan 030013,China;Shanxi Medical University,Taiyuan 030000,China)

机构地区：[1]山西医科大学基础医学院,太原030000 [2]山西省肿瘤医院病理科,太原030013 [3]山西医科大学,太原030000

出　　处：《中国组织化学与细胞化学杂志》2022年第1期44-51,共8页Chinese Journal of Histochemistry and Cytochemistry

基　　金：国家自然科学基金面上项目(82172659);山西省重点研发计划(指南)项目(201603D321049)。

摘　　要：目的检测肿瘤浸润淋巴细胞(tumor infiltrating lymphocyte,TIL)相关因子和PD-L1在错配修复蛋白缺失(deficient mismatch repair,dMMR)结直肠癌(colorectal cancer,CRC)中的表达,探究其在dMMR结直肠癌中的意义。方法利用LinkedOmics数据库和PrognoScan数据库分析TIL相关因子CD4、CD8、TBX21、GATA3在CRC中的表达及与预后的关系;收集山西省肿瘤医院2016年6月至2018年7月确诊为dMMR结直肠癌56例,并随机选取同期93例错配修复蛋白完整(proficient mismatch repair,pMMR)结直肠癌病例作为对照。采用免疫组织化学染色检测149例结直肠癌组织中TIL相关因子和PD-L1的表达水平,结合临床病理资料及随访数据进行分析。结果dMMR组中的CD8和TBX21阳性TIL数量高于对照组,CRC错配修复蛋白状态与肿瘤部位、大小、分化程度、浸润深度、PD-L1表达水平密切相关。多因素Cox回归分析显示TIL中TBX21的低表达是影响dMMR结直肠癌患者预后的危险因素,且Spearman相关性分析显示TBX21与PDL1的表达呈正相关。结论dMMR结直肠癌的肿瘤浸润淋巴细胞数量更多,拥有更加活跃的肿瘤微环境。TBX21结合PDL1有望能够成为dMMR结直肠癌预后评估新的指标。Objective To detect the expression of tumor infiltrating lymphocyte(TIL)-related factors and PD-L1 in mismatch repair protein deficient(dMMR)colorectal cancer(CRC)and to investigate their significance in dMMR colorectal cancer.Methods LinkedOmics database and PrognoScan database were used to analyze the expression of TIL-related factors,CD4,CD8,TBX21 and GATA3,in CRC and their relationship with CRC prognosis.Tissue samples from fifty-six cases of dMMR colorectal cancer diagnosed in Shanxi Cancer Hospital from June 2016 to July 2018 were collected,and tissue samples of 93 cases with proficient mismatch repair(pMMR)colorectal cancer in the same period were randomly selected as a control.Immunohistochemical staining method was used to detect the expression levels of TIL-related factors and PD-L1 in 149 colorectal cancer tissues,which were analyzed together with the clinicopathological data and follow-up data.Results The number of CD8 and TBX21 positive TILs was higher in the dMMR group than that in the control group,and CRC mismatch repair protein state was closely correlated with tumor site,size,degree of differentiation,depth of infiltration,and PD-L1 expression level.Multifactorial Cox regression analysis showed that low expression of TBX21 in TILs was a risk factor for prognosis in patients with dMMR colorectal cancer,and Spearman correlation analysis showed a positive correlation between TBX21 expression and PD-L1 expression.Conclusion dMMR colorectal cancer has a higher number of tumor infiltrating lymphocytes and possesses a more active tumor microenvironment.TBX21 combined with PD-L1 is expected to be a new indicator for prognostic assessment of dMMR colorectal cancer.

关 键 词：结直肠癌 错配修复蛋白 肿瘤微环境 肿瘤浸润淋巴细胞 PD-L1 

分 类 号：R735.3[医药卫生—肿瘤]