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

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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（qRT-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。

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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

Abstract：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 in 70 paraffin-embedded lung adenocarcinoma tissue samples and the corresponding para-carcinoma tissue using Taqman-based quantitative RT-PCR assays (qRT-PCR). The EGFR gene exons 19 and 21 of tumor tissue were amplified by PCR, followed by direct sequencing in 70 paraffin-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 in 24 cases of 70 (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.

Key words： epidermal growth factor receptor microRNA-135b lung neoplasms adenocarcinoma invasion epidermal growth factor receptor tyrosine kinase inhibitors

收稿日期: 2016-04-26

基金资助: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）。

通讯作者: 陈晓明，教授，Email：xmchen01@163.com。

作者简介: 王小灵（1989-），男，山西介休人，硕士生。

链接本文:

https://xb.wmu.edu.cn/CN/ 或 https://xb.wmu.edu.cn/CN/Y2017/V47/I4/248

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