非小细胞肺癌热毒证与基因突变及表皮生长因子酪氨酸激酶抑制剂疗效的相关性  

Correlation of toxic-heat pattern with the genetic alterations and efficacy of EGFR-TKI in non-small cell lung cancer patients

作　　者：朱燕娟[1,2,3,4] 曲鑫 陈惠惠[5] 詹丹丹 李海鹏 刘丽荣 刘译鸿[1] 李勇[1] 叶升[7] 张海波[3,4,8,9] ZHU Yan-juan;QU Xin;CHEN Hui-hui;ZHAN Dan-dan;LI Hai-peng;LIU Li-rong;LIU Yi-hong;LI Yong;YE Sheng;ZHANG Hai-bo(The Second Affiliated Hospital of Guangzhou University of Chinese Medicine(Guangdong Provincial Hospital of Traditional Chinese Medicine),Guangzhou 510120,China;The Second Clinical College of Guangzhou University of Chinese Medicine,Guangzhou 510120,China;Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome,Guangzhou 510120,China;Guangdong-Hong Kong-Macao Joint Lab on Chinese Medicine and Immune Disease Research,Guangzhou 510120,China;Zhuhai Hospital of Integrated Traditional Chinese and Western Medicine,Zhuhai 519020,China;Guangdong Agricultural Reclamation Central Hospital,Zhanjang 524018,China;The First Affiliated Hospital of Sun Yat-sen University,Guangzhou 510080,China;State Key Laboratory of Dampness Syndrome of Chinese Medicine,Guangzhou 510120,China)

机构地区：[1]广州中医药大学第二附属医院(广东省中医院),广州510120 [2]广州中医药大学第二临床医学院,广州510120 [3]广东省中医证候临床研究重点实验室,广州510120 [4]粤港澳中医药与免疫疾病研究联合实验室,广州510120 [5]珠海市中西医结合医院,珠海519020 [6]广东省农垦中心医院,湛江524018 [7]中山大学附属第一医院,广州510080 [8]省部共建中医湿证国家重点实验室,广州510120 [9]广州中医药大学第二附属医院(广东省中医院)肿瘤科,广州510120

出　　处：《中华中医药杂志》2022年第8期4756-4760,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：广州市健康医疗协同创新重大专项(No.201604020017);广东省科技计划项目(No.2017B030314166,No.2020B1212030006)。

摘　　要：目的:探索非小细胞肺癌(NSCLC)患者中医辨证分型与基因分型及表皮生长因子酪氨酸激酶抑制剂(EGFR-TKI)疗效的相关性。方法:诊断中医证型,二代基因测序技术检测肿瘤组织及血浆中168种肿瘤相关基因的变异情况,定期影像学随访EGFR-TKI治疗的NSCLC患者无疾病进展生存时间(PFS)和总生存时间,分析中医证候分型与基因分型及EGFR-TKI疗效的相关性。结果:共入组109例NSCLC患者,中医热毒证患者PIK3CA、MYC、PMS2以及NTRK1基因突变率显著高于非热毒证患者(P<0.05,P<0.01);PIK3CA突变为热毒证的独立相关因素(OR=3.72,P=0.047)。其中48例接受了EGFR-TKI治疗,中医热毒证(中位PFS:5.13月vs.10.20月,多因素分析HR=2.56,P=0.046)与RB1、PIK3CA、ERBB2突变共同组成独立的不良PFS相关因素。结论:NSCLC患者热毒证与PIK3CA基因突变显著相关,并且是EGFR-TKI治疗后的不良预后因素。Objective:To identify the correlation of the traditional Chinese medicine(TCM)patterns with the genetic alterations and efficacy of epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKI)in non-small cell lung cancer(NSCLC)patients.Methods:Using a next generation sequencing panel with 168 genes,matched tumor biopsy and plasma samples were detected.The progression free survival(PFS)and overall survival in EGFR-TKI treated patients were recorded by followup imaging.The correlation of TCM patterns with the genetic alterations was analyzed.Results:A total of 109 NSCLC patients were analyzed.There was a significant enrichment of PIK3CA,MYC,PMS2,and NTRK1 alterations in toxic-heat patients(P<0.05,P<0.01),where the PIK3CA alteration was independently associated with toxic-heat syndrome(OR=3.72,P=0.047).A total of 48 patients were treated with EGFR-TKI.Toxic-heat pattern(median PFS:5.13 months vs 10.20 months,HR=2.56,P=0.046),as well as the RB1,PIK3CA,and ERBB2 alterations were independently associated with poorer PFS after EGFR-TKI treatment.Conclusion:TCM toxic-heat pattern was associated with PIK3CA alteration in NSCLC patients and may predict poorer PFS in EGFR-TKI treated NSCLC patients.

关 键 词：中医证候 热毒证 基因变异 无疾病进展生存时间 非小细胞肺癌 

分 类 号：R273[医药卫生—中西医结合]