摘要
目的程序性死亡配体1(PD-L1)在结直肠癌(CRC)细胞的免疫逃逸过程中发挥关键作用。文中旨在探讨R0切除术后CRC患者接受卡培他滨为基础辅助化疗的无疾病生存期及总生存期的影响。方法回顾性分析2010年1月至2017年12月在郑州人民医院普通外科265例R0切除术后接受卡培他滨为基础辅助化疗的CRC患者。分析患者基线及接受治疗的预后资料。另收集患者外周血及术后部分癌组织标本分别进行PD-L1基因标记多态性位点的基因分型及PD-L1基因mRNA的表达测定。分析PD-L1基因多态性位点的基因型和其他变量的相关性。不同基因型患者的PD-L1基因mRNA表达通过非参检验分析,预后的单变量分析采用Kaplan-Meier生存分析方法,并通过Cox模型对其他变量进行校正。结果纳入研究的265例患者均可评价疗效,整体人群的中位无疾病生存期(mDFS)为4.6年,中位总生存期(mOS)为6.5年。纳入研究的PD-L1多态性位点均经过NCBI数据库查阅在中国人群中突变频率>10%的3个标记多态性位点(901T>C、-1813G>C和-1457T>A)。其中,在预后分析上仅发现901T>C位点存在显著的临床意义。PD-L1基因901T>C位点位于该基因内含子区域,在纳入研究的CRC患者中的分布频率为:TT型185例(69.81%)、TC型72例(27.17%)、CC型8例(3.02%),最小等位基因频率为0.17,3种基因型分布频率符合哈迪温伯格平衡(P=0.758)。由于CC基因型患者相对较少,将TC和CC型患者合并,两组基因型患者基线临床资料分布均衡。TT基因型和TC/CC基因型患者的mDFS分别为4.8和3.5年,差异有统计学意义(P=0.001)。2种基因型患者的mOS分别为6.7和4.7年,差异有统计学意义(P<0.001)。经过Cox模型校正OS后,TC/CC基因型对OS具有独立的影响意义(OR=1.89,P=0.006)。另外在89例癌组织标本的PD-L1 mRNA表达分析中发现,TC/CC型患者相对于TT基因型患者,癌组织中PD-L1的mRNA表达明显较高,差异有统计学意义(P<0.001)。结论 PD-L1基因901T>C位点可能通过介导PD-L1基因mRNA的表达影响接受卡培他滨为基础辅助化疗的CRC患者预后。
Objective Programmed death-ligand 1(PD-L1)is essential in the immune escape of colorectal cancer(CRC)cells.In this study,we investigated the disease-free survival(DFS)and overall survival(OS)of CRC patients receiving capecitabinebased adjuvant chemotherapy after RO resection.Methods This retrospective study included 265 CRC patients treated by RO resection and postoperative capecitabine-based adjuvant chemotherapy in Zhengzhou People's Hospital between January 1,2010 and December 12,2017.We analyzed the clinical data,performed genotyping of the genetic variants and determined the expression of PD-L1 mRNA in the CRC tissue.We also analyzed the correlation between the genetic polymorphisms and other baseline characteristics by chi-square test,the expression of PD-L1 mRNA in different genotypes by non-parametric test,and the prognosis using the Kaplan-Meier method,followed by multivariate Cox regression analysis for adjustment.Results The median DFS and OS of the 265 CRC patients were 4.6 and 6.5 years,respectively.Three single nucleotide polymorphisms of the PD-L1 gene,901T>C,-1813G>C and-1457T>A,were identified in the NCBI database with the minor allele frequency>10%in the Chinese population,of which,only 901T>C was of clinical significance in the outcome analysis.901T>C was located in the intron region of the PD-L1 gene,with the genotypes of TT in 185 cases(69.81%),TC in 72(27.17%)and CC in 8(3.02%).The minor allele frequency was 0.17 and the distribution frequencies of all the three genotypes conformed to the Hardy-Weinberg equilibrium(P=0.758).The median DFS was significantly longer in the CRC patients with the TT genotype than in those with the TC or CC genotype(4.8 vs 3.5 years,P=0.001),and so was the median OS(6.7 vs 4.7 years,P<0.001).The adjustment of OS by multivariate Cox regression analysis showed that the TC and CC genotypes were an independent factor for OS(OR=1.89,P=0.006).The analysis of 89 of the CRC tissue specimens revealed a markedly higher expression of PD-L1 mRNA in the patients with the TC or CC genotype than in those with the TT genotype(P<0.001).Conclusion The 901T>C polymorphism of the PD-L1 gene may influence the clinical outcomes of the CRC patients receiving capecitabine-based adjuvant chemotherapy by mediating the expression of PD-L1 mRNA.
作者
张宇
王敏
侯艳华
张俊杰
ZHANG Yu;WANG Min;HOU Yan-hua;ZHANG Jun-jie(Department of Third General Surgery,People's Hospital of Zhengzhou,Zhengzhou 450003,Henan,China;Department of Anesthesiology,the People's Hospital of Henan Province,Zhengzhou 450000,Henan,China)
出处
《医学研究生学报》
CAS
北大核心
2019年第4期391-396,共6页
Journal of Medical Postgraduates
基金
郑州市科技发展计划项目(20150079)
关键词
结直肠癌
程序性死亡配体1
多态性
预后
colorectal cancer
programmed death-ligand 1
polymorphism
prognosis
作者简介
通信作者:张俊杰,E-mail:zhangyucmu@163.com.
