miR-221及miR-222在非小细胞肺癌中的表达及其意义

The expression of miR-221 and miR-222 in non-small cell lung cancer and their significances

目的：分析miR-221、miR-222在非小细胞肺癌（NSCLC）组织中的表达情况，探讨其与患者临床病理特征及预后的关系。方法收集南华大学附属第一医院2012年2月至2014年5月手术治疗的55例NSCLC患者和10例肺良性病变患者（对照组）的石蜡标本和临床资料，所有患者进行术后随访。实时荧光定量PCR检测miR-221、miR-222的表达，分析其与临床病理特征和无进展生存（PFS）的关系，比较miR-221、miR-222高表达组和低表达组之间生存率的差异，采用Cox风险比例回归分析影响NSCLC预后的因素。结果 miR-221、miR-222在NSCLC组织中的表达水平分别为对照组的3.52倍和2.01倍（均P=0.000）。miR-221、miR-222表达与NSCLC的分化程度呈负相关（r=-0.732，P=0.000；r=-0.451，P=0.001），miR-221与miR-222表达呈正相关（r=0.376，P=0.000）。miR-221或miR-222高表达组的中位PFS均较低表达组明显缩短（miR-221：55.43周比81.29周，P=0.028；miR-222：45.00周比87.05周，P=0.008）。Cox多因素分析显示，miR-222高表达是NSCLC患者PFS的独立危险因素（RR=2.808，P=0.033）。结论 miR-221、miR-222在NSCLC组织中高表达并且二者呈正相关；miR-221、miR-222表达与NSCLC分化程度呈负相关。miR-221、miR-222高表达是NSCLC潜在的预后判断生物标志物。

Objective To explore the expression of miR-221/222 in non-small cell lung cancer （NSCLC） and its correlation with clinical pathological parameters. Methods The clinical pathological data and formalin fixed-paraffin embedded （FFPE） tissues of 55 NSCLC patients and 10 benign lesion patients who underwent surgery in the First Affiliated Hospital of Nanhua University from February 2012 to May 2014 were collected and followed. The relationship between miR-221/222 expression detected by real-time PCR and clinical pathological parameters and progression-free survival （PFS） were analyzed. The differential survival between the high expression group and the low expression group of miR-221/222 were compared. A Cox proportional hazard regression model was utilized to examine the prognostic factors of NSCLC. Results The expression level of miR-221/222 was significantly higher in tumor tissues than that in corresponding benign lesion tissues （Fold change=3.52, P=0.000;Fold change=2.01, P=0.000）. There was a negative correlation between miR-221/222 expression and pathological grades （r=-0.732, P=0.000;r=-0.451, P=0.001）. The relative expression of miR-221 showed a positive correlation with miR-222 （r=0.376, P=0.000）. Patients with higher levels of miR-221/222 were closely associated with a shorter PFS （miR-221： 55.43 weeks vs. 81.29 weeks, P=0.028; miR-222： 45.00 weeks vs. 87.04 weeks, P=0.008）. Finally, multivariate analysis demonstrated that miR-222 expression was independently associated with poor PFS （RR=2.808, P=0.033）. Conclusions miR-221/222 is highly expressed in NSCLC tumor tissues with a positive correlation. A negative correlation is observed between the expression of miR-221/222 and tumor differentiation. The potential high expression of miR-221/222 is considered as tumor biomarkers for the prognosis of NSCLC patients.