天津医药

天津医药 ›› 2016, Vol. 44 ›› Issue (3): 336-341.doi: 10.11958/20150331

• 临床研究 • 上一篇    下一篇

非吸烟女性肺腺癌组织中 miRNAs 的表达与表皮生长因子受体关系的研究

王富民1,张寰2,许芳秀1,曲金立1,孔金玉1,钱碧云3   

  1. 1 天津医科大学肿瘤医院， 肿瘤研究所肿瘤分子流行病与生物统计研究室， 国家肿瘤临床研究中心， 天津市肿瘤防治重点实验室（邮编 300060）；2天津医科大学研究生院；3 上海交通大学公共卫生学院；4上海交通大学医学院虹桥国际医学研究院
  • 收稿日期:2015-11-19 修回日期:2015-12-07 出版日期:2016-03-15 发布日期:2016-03-15
  • 通讯作者: 钱碧云 E-mail:wangfumin57@163.com
  • 作者简介:王富民(1988)， 男， 硕士在读， 主要从事肿瘤分子流行病学研究
  • 基金资助:
    国家自然科学基金资助项目（81573231）；天津市自然科学基金资助项目（13JCYBJC23100）

Study on the relationship between expression of miRNAs and receptors of epidermal growth factor in lung adenocarcinoma of non-smoking female

WANG Fumin1, 2, ZHANG Huan1, XU Fangxiu1, QU Jinli1, KONG Jinyu1, QIAN Biyun   

  1. 1 Department of Epidemiology and Biostatistics, Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China; 2 Graduate School of Tianjin Medical University； 3 Public Health, Shanghai Jiao Tong University School; 4 Hongqiao International Institute of Medicine,Shanghai Jiao Tong University School of Medicine
  • Received:2015-11-19 Revised:2015-12-07 Published:2016-03-15 Online:2016-03-15
  • Contact: QIAN Biyun E-mail:wangfumin57@163.com

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摘要： 目的 探讨非吸烟女性肺腺癌(ADC)组织中 miR-155、miR-16、miR-25 及 miR-133a 的表达与表皮生长因子受体（EGFR）的关系及其临床意义。 方法 112 例非吸烟女性 ADC 患者按 EGFR 类型分为 EGFR 野生型组（n= 51）和 EGFR 突变型组（n=61）。 用实时荧光定量 PCR 定量检测 2 组 ADC 组织中 4 种 miRNAs 的表达量， 比较 2 组 4 种 miRNAs 表达水平的差异。 4 种 miRNAs 表达量以平均数分层为高表达组和低表达组， 比较 2 亚组患者间的生存差异。 按年龄（≤60 岁， ＞ 60 岁）、EGFR 类型和 miRNAs 的表达量分层， 进行 Kaplan-Meier 生存分析和 Cox 比例风险回归模型检验。 结果 EGFR 突变型组 miR-25 的表达水平高于 EGFR 野生型组（P < 0.05）。 不同年龄分层、不同 EGFR 类型组、miR-155、miR-16 及 miR-133a 表达量患者的生存率差异无统计学意义， miR-25 低表达者的生存率较高表达者更高（P < 0.05）。 在 EGFR 突变型组中 4 种 miRNAs 的表达量与 ADC 预后无关（P > 0.05）； 在 EGFR 野生型组中 miR-16、miR-25、miR-133a 低表达者较高表达者生存率更高（P < 0.05）。 Cox 比例风险回归分析显示， miR-25 高表达是非吸烟女性 ADC 患者预后死亡的独立危险因素（P < 0.05）。 结论 miR-25 是非吸烟女性 ADC 的独立预后指标。 miR-25 在非吸烟女性 ADC， 特别是在 EGFR 野生型的患者中表达升高， 可能提示患者预后不佳。

关键词: 受体, 表皮生长因子, 吸烟, 性别因素, 基因表达, 肺腺癌, miR-155, miR-16, miR-25, miR-133a

Abstract: Objective To determine association between the expression of miR-155, miR-16, miR-25 and miR-133 and epidermal growth factor receptor (EGFR) in lung adenocarcinoma (ADC) samples of non-smoking female, and their clini⁃ cal significance thereof. Methods According to EGFR types, 112 non-smoking female ADC patients were divided into two groups: EGFR wild (n=51) and EGFR mutant (n=61) groups. Expression levels of four miRNAs were detected by real time quantitative PCR. T-test was used to compare differences of four miRNAs expression in two groups. ADC patients were divid⁃ ed into high miRNA expression group and low expression group according to the mean value of miRNAs expression. Logrank test was used to compare the survival difference between the two subgroups. Cox proportional hazards regression analy⁃ sis was performed to determine the association between different ages (≤60， >60), EGFR types, miRNAs expression and over⁃ all survival. Results The expression of miR-25 was significantly higher in EGFR mutant group than that in EGFR wild group (P < 0.05). There were no significant differences in the survival rates of patients with different ages, EGFR types, and the expressions of miR-155, miR-16 and miR-133a. Patients with the lower expression of miR-25 had the higher survival time than patients with the higher expression of miR-25 (P < 0.05). In EGFR mutation group, there was no relationship be⁃ tween four miRNAs and the prognosis of ADC (P > 0.05). In EGFR wild group, the lower expression of miR-16, miR-25 or miR-133a was associated with longer survival in ADC (P < 0.05). Cox proportional hazards regression analysis revealed that the high expression of miR-25 was an independent risk factor for non-smoking female patients with ADC (P < 0.05). Con⁃ clusion miR-25 is an independent prognostic indicator for non-smoking female patients with ADC. High expression of miR-25 is found in non-smoking female patients with ADC, particularly in patients with EGFR wild-type, which may sug⁃ gest a poor prognosis.

Key words: receptor, epidermal growth factor, moking, sex factors, gene expression, lung adenocarcinoma, miR-155, miR-16, miR-25, miR-133a