摘要
背景与目的:结直肠癌是常见的消化道肿瘤之一,中国的结直肠癌发病率和死亡率都位居前列。循环肿瘤DNA(circulating tumor DNA,ctDNA)作为一种非侵入性检测标志物在结直肠癌患者全病程管理中具有一定价值。通过对转移性结直肠癌(metastatic colorectal cancer,mCRC)患者血浆ctDNA中相关基因突变状态进行检测和分析,可协助制定患者个性化治疗方案。方法:本研究纳入2016年6月—2017年1月复旦大学附属中山医院收治的30例mCRC患者,利用二代测序(next generation sequencing,NGS)和MALDI-TOF检测患者血浆ctDNA中KRAS、NRAS、BRAF、PIK3CA基因的常见突变。将两个平台数据相互比较,同时结合病史、组织活检结果和微滴式数字聚合酶链反应(droplet digital polymerase chain reaction,ddPCR)得到的结果进行比较,评估本实验中NGS和MALDI-TOF检测的结果与综合获得的结果的符合率以及各自的阳性预测值和阴性预测值。结果:MALDI-TOF的符合率为76.67%,阳性预测值为86.67%,阴性预测值为66.67%。NGS的符合率为86.67%,阳性预测值为83.33%,阴性预测值为91.67%。结论:两个平台均可用于检测ctDNA中的常见突变,但NGS的阴性预测值要优于MALDI-TOF,同时突变位点丰度与原发灶是否手术切除以及患者是否接受过治疗有关。
Background and purpose:Colorectal cancer is one of the common gastrointestinal tumors.The incidence and mortality of colorectal cancer in China are high.Circulating tumor DNA(ctDNA)has a certain value in the whole course of the medical management of patients with colorectal cancer as a non-invasive detection marker.The status of related gene mutations in plasma ctDNA of patients with metastatic colorectal cancer(mCRC)were detected and analyzed to assist in making personalized treatment plan for patients.Methods:This study included 30 patients with mCRC who were treated in Zhongshan Hospital,Fudan University from June 2016 to January 2017,using next generation sequencing(NGS)and nucleic acid mass spectrometry to detect ctDNA mutations,and compared the performance of these two platforms.The above two platforms were used to detect common mutations in gene KRAS,NRAS,BRAF and PIK3CA from ctDNA extracted from plasma of mCRC patients.Meanwhile,the results obtained from two platforms were compared with the results combining the history,biopsy and droplet digital polymerase chain reaction(ddPCR)results to evaluate the detection coincidence rate,specificity and sensitivity of these two platforms.Results:The coincidence rate of nucleic acid mass spectrometry was 76.67%,the sensitivity was 86.67%,and the specificity was 66.67%.The coincidence rate of NGS was 86.67%,the sensitivity was 83.33%,and the specificity was 91.67%.Conclusion:Both platforms can be used to detect common mutations in ctDNA,but the negative predictive value of NGS is better than that of MALDI-TOF.Meanwhile,the mutation abundance of mutation sites is related to whether the patient’s primary tumor is resected and whether the patient has been treated.
作者
陈馨宁
黄斐
沈敏娜
杨轶慧
王蓓丽
郭玮
CHEN Xinning;HUANG Fei;SHEN Minna;YANG Yihui;WANG Beili;GUO Wei(Department of Laboratory Medicine,Zhongshan Hospital,Fudan University,Shanghai 200032,China;Department of Laboratory Medicine,Xiamen Branch,Zhongshan Hospital,Fudan University,Xiamen 361015,Fujian Province,China)
出处
《中国癌症杂志》
CAS
CSCD
北大核心
2021年第3期192-197,共6页
China Oncology
基金
国家自然科学基金(81772263,81972000,81902139)
2019厦门市医疗卫生重点项目(YDZX20193502000002)
复旦大学附属中山医院临床研究专项基金(2018ZSLC05)
上海市临床重点专科建设项目(医学检验科)。