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

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.