ERCC1 mRNA表达与结直肠癌标准方案化疗临床预后的相关性研究

摘要

目的：：探讨结直肠癌石蜡组织中切除修复交叉互补基因( excision repair cross-complementing group 1,ERCC1) mRNA表达水平与接受标准方案化疗的结直肠癌患者临床病理的关系以及其预后意义。方法：采用实时荧光定量 RT-PCR检测福尔马林固定-石蜡包埋的结直肠癌组织中DNA修复基因ERCC1 mRNA的表达水平,并比较其表达水平与接受标准方案化疗的结直肠癌患者的临床病理及生存期之间的关系。结果：ERCC1 mRNA表达与结直肠癌临床病理特征无相关性(P>0.05)。将ERCC1 mRNA在96例大肠癌患者中的表达量(相对于β-actin)分为低表达组与中高表达组(≤5.21为低表达组,>5.21为中高表达组),样本总生存期呈正态分布,中高表达组平均总生存期为68.52月(95%CI：63.06-76.06),低表达组平均总生存期为56.63月(95%CI：44.45-68.80),从生存曲线上看中高表达组患者总生存时间明显长于低表达组,两者有统计学差异(P=0.049)。样本无进展生存期呈偏态分布,中高表达组的中位生存时间30.98月(95%CI：0-18.65),低表达组的中位生存时间8.48月(95%CI：6.37-10.60),两者之间差别无统计学意义(P=0.575)。 Cox多因素回归分析发现性别(P=0.023)、分期(P<0.001)、以肠梗阻或肠穿孔起病(P=0.046)是患者总生存期的独立影响因素,年龄(P=0.043)、分期(P<0.001)、脉管侵犯(P=0.002)是患者无进展生存期的独立影响因素。结论：ERCC1 mRNA的表达水平可能是使用标准方案化疗的结直肠癌患者预后的影响因素,性别、分期、以肠梗阻或肠穿孔起病、年龄、脉管侵犯是影响结直肠患者预后的独立影响因素。%Objective:To investigate the correlation of the mRNA expression levels of excision repair cross-com-plementing group 1 ( ERCC1 ) with clinicopathological parameters in patients with colorectal cancer receiving the standard first-line chemotherapy regimens as well as their clinical prognostic significance. Methods:The relative mR-NA expression of ERCC1 in formalin-fixed paraffin-embeded colorectal cancer tumor specimens was measured using quantitative reverse transcription polymerase chain reaction. And the relationship between ERCC1 levels with clinico-pathological parameters and survival in colorectal cancer was studied. Results:ERCC1 expression was not related to clinicopathological parameters in colorectal cancer(P>0. 05). Though from multivariate analysis,the time of average overall survival in middle-high group of ERCC1 mRNA expression was 68. 52 months,low group was 56. 63months. ERCC1 mRNA hypoexpression was a significantly favorable factor for overall survival(P=0. 049),not for time to progression (P=0. 575). From Cox proportional hazards model for survival,sex(P=0. 023),stage(P<0. 001),intestinal obstruc-tion or perforation as initial symptom(P=0. 046) were independent predictive markers of overall survival of colorectal cancer.Age(P=0.043),stage(P<0.001),vesselinvasion(P=0.002) were independent predictive markers of progression free survival. Conclusion:It was suggested that intratumoral ERCC1 mRNA expression level be a predictive marker of survival of the standard first-line chemotherapy regimens in colorectal cancer. Sex,stage,intestinal obstruction or perfo-ration as initial symptom,age,vessel invasion were independent predictive markers of colorectal cancer.