摘要
目的探究晚期结直肠癌患者基因突变特征及循环肿瘤DNA(ctDNA)动态监测对中药干预治疗疗效的预测作用。方法采用前瞻性的研究方法,筛选在中国中医科学院西苑医院肿瘤科接受中医药治疗的,行NGS检测(Next-generatio sequencing technology)的晚期结直肠癌病例,利用卡方检验(χ2)对晚期结直肠癌患者的基因突变情况与疾病相关信息进行相关性分析,P<0.05为差异有统计学意义;筛选行4次及以上ctDNA动态监测的病例进行ctDNA动态变化趋势与中医干预治疗疗效相关性分析。结果研究共纳入69例晚期结直肠癌患者,血浆ctDNA基因突变检出率为81%,基因突变频率排在前三位的依次为TP53(83.6%),APC(72.1%),KRAS(53.4%);ctDNA与肿瘤组织配对检测样本42例,组织基因突变与血浆ctDNA匹配率为76%;临床相关因素分析显示:TP53、APC、PIK3CA基因突变与是否发生肝转移显著相关(P<0.05),ERBB2基因突变与肝郁脾虚证型、肝肾亏虚证型显著相关(P<0.05);对9例行过4次及以上ctDNA与CEA、CT同时检测的患者,进行ctDNA动态变化趋势与中药干预治疗疗效相关性探讨,发现ctDNA突变丰度变化趋势与中药干预治疗晚期结直肠癌的疗效高度吻合,部分结果显示ctDNA具有提前CEA和影像学预示肿瘤进展的趋势。结论TP53、APC基因突变的结直肠癌患者易发生肝转移,PIK3CA基因突变的患者不易发生肝转移,ERBB2基因突变可能与肝郁脾虚证型、肝肾亏虚证型相关;相较于传统的CEA与影像学检查,外周血ctDNA动态监测可提前预测晚期结直肠癌的中药干预治疗疗效,从而更好的指导晚期结直肠癌的中医药治疗。
Objective To explore the predictive effect of gene mutation characteristics and circulating tumor DNA(ctDNA) dynamic monitoring on the efficacy of traditional Chinese medicine(TCM) intervention in patients with metastatic colorectal cancer(mCRC).Methods Using prospective research methods,Sixty-nine patients with mCRC who voluntarily accepted NGS test and received TCM treatment were screened.The chi-square test was used to analyze the correlation between gene mutation and disease-related information of 43 patients with mCRC who received tissue samples for examination.P0.05 was considered statistically significant.Patients who had undergone four or more times of ctDNA dynamic monitoring were screened to analyze the correlation between the dynamic change trend of ctDNA and the therapeutic effect of TCM intervention.Results A total of 69 patients with mCRC were included in this study.The detection rate of ctDNA gene mutation was 81%,and TP53(83.6%),APC(72.1%) and KRAS(53.4%) were the top three mutation frequencies.The matching rate of tissue gene mutation and ctDNA was 76%.Analysis of clinical factors showed that TP53,APC and PIK3CA gene mutations were significantly correlated with the occurrence of liver metastasis(P0.05).The ERBB2 gene mutations were significantly correlated with the syndrome type of liver depression and spleen deficiency or deficiency of liver and kidney(P0.05).For 9 patients with mCRC who had been detected ctDNA,CEA and CT for more than 4 times,the correlation between the dynamic change trend of ctDNA and the therapeutic effect of TCM intervention was discussed.It was found that the change trend of ctDNA mutation abundance was highly consistent with the therapeutic effect of TCM intervention in the treatment of mCRC.Some results showed that ctDNA had the trend of predicting tumor progression in advance of CEA and imaging.Conclusion ctDNA has a high detection rate in mCRC patients and a high matching degree with tumor tissue.Patients with TP53 and APC gene mutations are prone to liver metastasis,while those with PIK3CA gene mutations are not prone to liver metastasis.The mutation of ERBB2 gene was associated with the syndromes of liver depression and spleen deficiency or deficiency of liver and kidney.ctDNA liquid biopsy can monitor clinical therapeutic efficacy and tumor condition in real time,and may predict tumor progression in advance more than CEA and imaging,so as to better guide the TCM treatment of mCRC.
作者
徐钰莹
杨宇飞
易丹辉
Xu Yuying;Yang Yufei;Yi Danhui(Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100091,China;School of Statistics,Renmin University of China,Beijing 100872,China)
出处
《世界科学技术-中医药现代化》
CSCD
北大核心
2023年第1期286-298,共13页
Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology
基金
首都卫生发展科研专项项目(2016-1-4171):真实世界注册研究基础上的晚期消化道恶性肿瘤幸存者中医优势人群特征分析,负责人:杨宇飞
国家中医药管理局中医药传承与创新“百千万”人才工程(2018-288):岐黄工程,负责人:杨宇飞。
关键词
晚期结直肠癌
循环肿瘤细胞DNA
基因突变
中药
治疗疗效
Metastatic Colorectal cancer
Circulating tumor DNA
Gene mutation
Traditional Chinese medicine
Treatment efficacy
