晚期非小细胞肺癌靶向治疗耐药与HOTAIR基因表达及中医证候分型的关系

An Observation on Relationship Between Targeted Therapy and Drug Resistance in Advanced Non-Small Cell Lung Cancer and HOTAIR Gene Expression and Chinese Medicine Syndrome Types

目的:观察晚期非小细胞肺癌(NSCLC)患者用表皮生长因子受体-酪氨酸激酶抑制剂(EGFR-TKIs)治疗耐药后患者组织、血清中HOX转录反义RNA(HOTAIR)基因表达与中医证候分布特点及疗效的相关性,为靶向治疗后的非小细胞肺癌患者提供中医辨证论治依据。方法:选择2017年3月—2019年4月期间经病理组织学确诊的89例晚期NSCLC患者,进行EGFR-TKIs治疗,并进行中医辨证分型,治疗前后采集肿瘤组织及血清学标本,检测EGFR-TKIs治疗前后、耐药后患者肿瘤组织、血清HOTAIR水平,分析晚期NSCLC患者EGFR-TKIs治疗与HOTAIR基因表达及中医证候分布特点的相关性。结果:NSCLC患者进行EGFR-TKIs治疗2个月后患者肿瘤组织及血清中HOTAIR相对表达量低于治疗前,差异均有统计学意义(P<0.05);EGFR-TKIs耐药患者肺肿瘤组织及血清中HOTAIR相对表达量高于EGFR-TKIs非耐药患者,差异均有统计学意义(P<0.05)。EGFR-TKIs耐药患者中医证候分型以阴虚血瘀证、气阴两虚证为主,非耐药患者证候分型以气虚血瘀证、气虚痰湿证为主,其证候分布差异有统计学意义(P<0.05)。结论:非小细胞肺癌EGFR-TKIs治疗及耐药均与HOTAIR基因表达相关,EGFR-TKIs治疗对非小细胞肺癌患者中医证候分布有影响。

Objective:To observe the gene expression of HOX transcript antisense RNA(HOTAIR)in serum and in tissues,the distribution of Chinese medicine syndromes,therapeutic effect,and their internal relationship in patients with advanced non-small cell lung cancer(NSCLC)who were treated by epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs)and were resistant to the drug;and to provide the basis of Chinese medicine syndrome differentiation for NSCLC patients after targeted therapy.Methods:A total of 89 patients with advanced NSCLC diagnosed by histophiology from March 2017 to April 2019 were selected for EGFR-TKIs treatment and were differentiated according to the Chinese medicine syndrome types.Tumor tissues and serological specimens were collected before and after treatment;the HOTAIR levels in them were detected before and after EGFR-TKIs treatment and after drug resistance;the relationship between the EGFR-TKIs treatment and HOTAIR gene expression and distribution of Chinese medicine syndrome was analyzed.Results:After two months of EGFR-TKIs treatment,the relative expression of HOTAIR in tumor tissues and serum of NSCLC patients was lower than that before treatment,differences being significant(P<0.05).The relative expression of HOTAIR in tumor tissues and serum of patients with EGFR-TKIs resistance was higher than that of patients without EGFR-TKIs resistance,differences being significant(P<0.05).The Chinese medicine syndromes of patients with EGFR-TKIs resistance were mainly yin deficiency and blood stasis syndrome and dual deficiency of qi and qi syndrome;the Chinese medicine syndromes of patients without EGFR-TKIs resistance were mainly qi deficiency and blood stasis syndrome and qi deficiency and phlegm dampness syndrome,the difference being significant(P<0.05).Conclusion:Both EGFR-TKIs treatment and drug resistance for NSCLC patients are related to the gene expression of HOTAIR,and EGFR-TKIs treatment has an impact on the distribution of Chinese medicine syndromes in NSCLC patients.