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

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

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。

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. Log- rank 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 survivaltime 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.