海岛地区肺腺癌microRNA-135b与表皮生长因子受体基因突变的相关性  

The correlative analysis between microRNA-135b and EGFR mutation status in lung adenocarcinoma of Zhoushan Archipelago

作　　者：王小灵[1] 查瑶 马海洁[1] 竺王玉[1] 张永奎[2] 陈晓明[3] WANG Xiaoling;ZHA Yao;MA Haijie;ZHU Wangyu;ZHANG Yongkui;CHEN Xiaoming(Laboratory of Cytobiology and Molecular Biology, Zhoushan Hospital Affiliated to Wenzhou Medical University, Zhoushan, 316000;Department of Cardio-Thoracic Surgery, Zhoushan Hospital Affiliated to Wenzhou Medical University, Zhoushan, 316000;School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, 325035)

机构地区：[1]温州医科大学附属舟山医院细胞分子生物学实验室,浙江舟山316000 [2]温州医科大学附属舟山医院胸心外科,浙江舟山316000 [3]温州医科大学检验医学院生命科学学院,浙江温州325035

出　　处：《温州医科大学学报》2017年第4期248-253,共6页Journal of Wenzhou Medical University

基　　金：浙江省医药卫生重大科技项目(WKJ2014-2-021);浙江省医药卫生平台计划(重点资助)项目(2015;ZDA032);舟山市公益类科技项目(2015C31029)

摘　　要：目的:通过检测舟山海岛地区肺腺癌患者组织中microRNA-135b(miR-135b)与表皮生长因子受体(EGFR)的突变情况,分析二者之间的相关性,找到指导EGFR酪氨酸激酶抑制剂(EGFR-TKIs)用药的新指标。方法:运用实时荧光定量PCR(q RT-PCR)检测70例石蜡包埋肺腺癌组织和癌旁组织中miR-135b的表达水平;运用PCR扩增产物直接测序法检测以上肿瘤组织中EGFR 19、21外显子突变情况。结果:miR-135b在肺腺癌组织中的表达水平高于癌旁组织(P<0.01),且在侵袭性组(IAC)的表达水平要显著高于非侵袭性组(AIS/MIA)中的表达水平(P<0.01);70例肿瘤组织中,共有24例(占34.3%)发生EGFR突变,而侵袭性组(IAC)中EGFR的突变率(为53.3%)要高于非侵袭性组(AIS/MIA)中的突变率(为20%)。统计分析结果表明miR-135b在EGFR突变组的表达水平要显著高于EGFR野生组(P<0.05)。结论:EGFR突变和miR-135b的表达水平与肺腺癌的侵袭性正相关,两者可用来评估肺腺癌的进展;EGFR突变的肺腺癌患者其miR-135b表达水平高,miR-135b或许可以作为预测EGFR-TKIs药物有效性的生物学指标,并有望成为改善EGFR-TKIs耐药的新靶点。Objective:To analyze the relationship between EGFR mutations and miR-135b in lung adenocarcinoma of Zhoushan Archipelago and find new indicator for the guidance of EGFR-TKIs.Methods:MiR-135b quantification was retrospectively detected in70paraffin-embedded lung adenocarcinoma tissue samples and the corresponding para-carcinoma tissue using Taqman-based quantitative RT-PCR assays(qRTPCR).The EGFR gene exons19and21of tumor tissue were amplified by PCR,followed by direct sequencing in70paraffin-embedded lung adenocarcinoma tissue.Results:MiR-135b was markedly up-regulated in lung adenocarcinomas in comparison to the corresponding para-carcinoma tissue(P<0.01)and miR-135b had a higher level in the group of invasive lung adenocarcinoma(IAC)compared to the group of noninvasive lung adenocarcinoma(adenocarcinoma in situ/minimally invasive adenocarcinoma,AIS/MIA)(P<0.01);EGFR mutations were detected in24cases of70(34.3%)patients with lung adenocarcinoma.The mutation rate in IAC(53.3%)was higher than that in AIS/MIA(20%).Patients harbouring EGFR mutations had higher miR-135b expression level,which indicated that miR-135b was positive correlation with EGFR mutations.Conclusion:EGFR mutations and miR-135b may be positive correlation with the invasion of lung adenocarcinoma and both of them can be used to assess the progress of lung adenocarcinoma.MiR-135b can be the biological marker for effectiveness evaluation of EGFR TKIs and is expected to become the new target for improving EGFR TKIs resistance.

关 键 词：表皮生长因子受体 microRNA-135b 肺肿瘤 腺癌 侵袭性 表皮生长因子受体酪氨酸激酶抑制剂 

分 类 号：R34[医药卫生—基础医学] R73-37