程序性死亡因子配体1与微卫星状态在低分化结直肠癌组织中的表达及临床意义

Expression and clinical significance of programmed death ligand 1 and microsatellite status in poorly differentiated colorectal cancer tissues

目的 探讨程序性死亡因子配体1(programmed death ligand 1,PD-L1)与微卫星状态(microsatellite status, MS)在低分化结直肠癌(colorectal cancer, CRC)组织中的表达及临床意义。方法 收集郑州大学第二附属医院2016年1月至2019年1月收治的89例CRC患者临床资料及石蜡标本,其中低分化腺癌49例(试验组);中高分化腺癌40例(对照组)。采用免疫组化法检测CRC组织的MS和PD-L1表达情况,评估低分化CRC MS及PD-L1表达与患者临床病理特征关系,采用Kaplan-Meier法分析低分化CRC患者MS及PD-L1表达水平与无病生存期(disease free survival, DFS)间关系,并利用Cox多因素分析对DFS危险因素进行评估。结果 CRC中MSI为17例,发生率为19.10%(17/89),试验组与对照组在肿瘤位置、临床分期、淋巴结转移、MS及PD-L1表达比较,差异有统计学意义(P<0.05)。低分化CRC组织中MS在肿瘤位置、淋巴结转移、T分期及临床分期比较,差异有统计学意义(P<0.05),在性别和年龄比较,差异无统计学意义(P>0.05)。低分化CRC组织中PD-L1表达在淋巴结转移的比较差异有统计学意义(P<0.05)。低分化CRC的MSI患者DFS明显长于MSS患者(P=0.016),低分化CRC的PD-L1-患者DFS明显长于PD-L1+患者(P=0.002),PD-L1+/MSS亚组DFS短于PD-L1-/MSS亚组和PD-L1-/MSI亚组(P<0.05)。结论 MS与PD-L1表达是评估CRC预后的重要指标,具有MSI的低分化CRC患者可获得较好的预后,PD-L1阳性表达是影响低分化CRC患者术后复发的独立危险因素。

Objective To investigate the expression and clinical significance of programmed death ligand 1(PD-L1)and microsatellite status(MS)in poorly differentiated colorectal cancer(CRC)tissues.Methods The clinical data and paraffin specimens of 89 patients with CRC admitted to the Second Affiliated Hospital of Zhengzhou University from Jan.2016 to Jan.2019 were collected.There were 49 cases of poorly differentiated adenocarcinoma(experimental group)and 40 cases of moderately and well-differentiated adenocarcinoma(control group).Immunohistochemistry was used to detect the expression of MS and PD-L1 in CRC tissues.The relationship between the expression of MS and PD-L1 in poorly differentiated CRC and the clinical symptoms of the patients was evaluated.The Kaplan-Meier method was used to analyze the relationship between MS and PD-L1 expression levels and disease-free survival(DFS)in poorly differentiated CRC patients,and the Cox multivariate analysis was used to evaluate the risk factors of DFS.Results There were 17 cases of MSI in CRC,and the incidence rate was 19.10%(17/89).There were significant differences between the experimental group and the control group in tumor location,vascular tumor thrombus,lymph node metastasis,MS and PD-L1 expression(P<0.05).There were significant differences in tumor location,lymph node metastasis,T stage and clinical stage of MS in poorly differentiated colorectal cancer tissues(P<0.05).The expression of PD-L1 in poorly differentiated CRC tissues was significantly different in lymph node metastasis(P<0.05).The DFS of MSI patients with poorly differentiated CRC was significantly higher than that of MSS patients(P=0.016),the DFS of PD-L1-patients with poorly differentiated CRC was significantly higher than that of PD-L1+patients(P=0.002),and the MS and PD-L1 patients with poorly differentiated CRC combined subgroup analysis found that DFS of PD-L1+/MSS subgroup was shorter than that of PD-L1-/MSS subgroup and PD-L1-/MSI subgroup(P<0.05).Conclusion MS and PD-L1 expression are important indicators for evaluating the prognosis of CRC.Poorly differentiated CRC patients with MSI can achieve better prognosis.PD-L1 positive expression is an independent risk factor for postoperative recurrence in poorly differentiated CRC patients.