结肠癌组织中PD-1、PD-L1表达及临床意义

Expressions and clinical significance of PD-1 and PD-L1 in colon cancer

目的探讨结肠癌组织中PD-1、PD-L1表达及其与临床病理特征及预后的关系,为结肠癌的治疗提供参考。方法收集2011年6月至2013年6月期间在本院行手术切除的结肠癌组织及对应距离病变组织5 cm以上的癌旁正常组织各85例,均经术后病理证实。采用免疫组化法和实时荧光定量PCR法检测结肠癌组织及癌旁组织中的PD-1、PD-L1蛋白和mRNA表达,分析PD-1、PD-L1蛋白表达与临床病理特征的关系,并分析PD-1、PD-L1蛋白表达与结肠癌预后的关系。结果结肠癌组织中PD-1、PD-L1蛋白阳性表达率明显高于癌旁组织,差异均有统计学意义(均P<0.05);结肠癌组织的PD-1 mRNA、PD-L1 mRNA表达量均明显高于癌旁组织,差异均有统计学意义(均P<0.05);肿瘤直径>3 cm、TNM分期为Ⅲ~Ⅳ、Ducks分期为C^D的PD-1、PD-L1阳性表达率明显高于肿瘤直径≤3 cm、TNM分期为Ⅰ~Ⅱ、Ducks分期为A^B,差异均有统计学意义(均P<0.05);PD-1阳性、PD-1阴性表达患者5年生存率分别为62.50%、79.49%,PD-1阳性患者5年生存率明显低于PD-1阴性者,差异有统计学意义(P<0.05);PD-L1阳性、PD-L1阴性表达患者5年生存率分别为61.36%、82.86%,PD-L1阳性者5年生存率明显低于PD-L1阴性者,差异有统计学意义(P<0.05)。结论PD-1/PD-L1通路是结肠癌免疫抑制的重要机制,通过药物阻断这一通路有利于增强患者机体免疫功能,提高结肠癌的治疗效果,改善其预后。

Objective To investigate the expressions of PD-1 and PD-L1 in colon cancer tissue and their relationship with clinicopathological features and prognosis,and to provide some references for the treatment of colon cancer.Methods The expressions of PD-1 and PD-L1 proteins and mRNA in resected colon cancer tissues and adjacent normal tissues collected from our hospital between June,2011 and June,2013 were detected by immunohistochemistry and real-time fluorescence quantitative PCR.The relationship between the expressions of PD-1 and PD-L1 proteins on one hand and clinicopathological characteristics on the other hand was analyzed.The relationship between the expressions of PD-1 and PD-L1 proteins on one hand and the prognosis of colon cancer on the other hand was analyzed.Results The positive expression rates of PD-1 and PD-L1 proteins in the colon cancer tissues were significantly higher than those in the adjacent tissues(both P<0.05).The expressions of PD-1 and PD-L1 mRNA in the colon cancer tissues were significantly higher than those in the adjacent tissues(both P<0.05).The positive expression rates of PD-1 and PD-L1 in the tumors with diameter>3cm,TNM stageⅢ-Ⅳ,and Ducks stage C-D were significantly higher than those in the tumors with diameter<3 cm,TNM stage I-Ⅱ,and Ducks stage A-B(all P<0.05).The 5-year survival rates of the patients with positive and negative PD-1 expressions were 62.50%and 79.49%,respectively;the 5-year survival rate of the patients with positive PD-1 expressions was significantly lower than that of the patients with negative PD-1 expression(P<0.05).The 5-year survival rates of the patients with positive and negative PD-L1 expressions were 61.36%and 82.86%,respectively;the 5-year survival rate of the patients with positive PD-L1 were significantly lower than that of the patients with negative PD-L1 expression(P<0.05).Conclusion PD-1/PD-L1 pathway is an important mechanism of immunosuppression in colon cancer.Drug blockade of this pathway is beneficial to enhance the patients’immune function,improve the therapeutic effect and prognosis.