一种新型聚合酶链反应法在结直肠癌患者靶向治疗辅助诊断中的价值  

Value of a novel polymerase chain reaction method in evaluating the efficacy of targeted therapy in patients with colorectal cancer

作　　者：刘彦魁 谈杞 王晓莉[1] 乔岩 张明东 齐晓薇[1] Liu Yankui;Tan Qi;Wang Xiaoli;Qiao Yan;Zhang Mingdong;Qi Xiaowei(Department of Pathology,the Affiliated Hospital of Jiangnan University,Wuxi 214122,China;Wuxi Medical School,Jiangnan University,Wuxi 214122,China;Microdiag Biomedical Technology Co.,Ltd,Suzhou 215123,China)

机构地区：[1]江南大学附属医院病理科,无锡214122 [2]江南大学无锡医学院,214122 [3]江苏为真生物医药技术股份有限公司,苏州215123

出　　处：《中华实验外科杂志》2022年第7期1371-1374,共4页Chinese Journal of Experimental Surgery

基　　金：无锡市卫生健康委科技计划(T202114);无锡市转化医学研究所项目(LCYJ202204)。

摘　　要：目的探索外周血和组织样本检测结直肠癌大鼠Kirsten肉瘤病毒基因同源基因(KRAS)的一致性,评估其指导结直肠癌患者靶向治疗的价值。方法收集2015年1月至2021年8月江南大学附属医院451例结直肠癌患者的外周血及手术切除的肿瘤组织样本;外周血进行IAMB检测,组织样本同时进行组织IAMB法和Sanger测序。并选择其中44例样本同时进行外周血NGS检测和组织参比试剂盒检测。分析不同方法检测患者外周血和组织KRAS基因状态的一致性。同时收集患者的临床病理特征和靶向治疗相关随访数据。不同检测方法检测结果差异的比较使用配对样本McNemar检验;外周血和组织样本的一致性检验使用Kappa检验。结果IAMB法和Sanger测序法检测结直肠癌组织样本KRAS基因的突变率分别为47.9%(216/451)、45.2%(204/451),IAMB法检测外周血中KRAS基因的突变率为39.0%(176/451),外周血和组织IAMB法检测的阳性符合率、阴性符合率、总符合率分别为72.2%(156/216)、91.5%(215/235)、82.3%(371/451)。1例组织样本未检测到KRAS基因突变而外周血检测到KRAS基因突变的患者接受西妥昔单抗治疗2个月后即发生进展,其疗效低于文献中的中位无进展生存期。结论外周血IAMB法检测结直肠癌患者KRAS基因有助于结直肠癌患者个体化治疗辅助诊断。Objective To explore the consistency of KRAS status in peripheral blood and tissue samples in colorectal cancer,and to evaluate the value of a new polymerase chain reaction(PCR)method which integrates Amplification block mutation system(ARMS),Melting curves and wild-type DNA Blocking(IAMB)in guiding targeted therapy in patients with colorectal cancer.Methods Peripheral blood and surgical tumor tissue samples of 451 colorectal cancer patients from January 2015 to August 2021 in the Affiliated Hospital of Jiangnan University were collected for IAMB testing separately,and tissue samples were also detected by Sanger sequencing.In addition,44 cases were selected for peripheral blood NGS and tissue reference kit.The consistency of KRAS gene status by different methods detected was analyzed.Patients’clinicopathological characteristics and follow-up data were also collected.McNemar test was used for paired samples in different testing methods.Kappa test was used for the concordance analysis of peripheral blood and tissue samples KRAS detecting.Results The mutation rates of KRAS gene in colorectal cancer tissue samples detected by IAMB method and Sanger sequencing method were 47.9%(216/451)and 45.2%(204/451),respectively.The mutation rate of KRAS gene in peripheral blood detected by IAMB method was 39.0%(176/451).The positive percent agreement,negative percent agreement and overall percent agreement of peripheral blood and tissue detected by IAMB method were 72.2%(156/216),91.5%(215/235)and 82.3%(371/451)respectively.One patient whose KRAS gene mutation was not detected in tissue samples but was detected in peripheral blood progressed after receiving cetuximab for 2 months,and the curative effect was worse than the median progression-free survival time of literature data.Conclusion Detection of KRAS gene using peripheral blood IAMB method can be an effective supplement to target treatment of colorectal cancer patients.

关 键 词：结直肠癌 靶向治疗 

分 类 号：R735.34[医药卫生—肿瘤]