食管鳞癌组织中miR-148a的表达及其临床意义

目的检测食管鳞癌组织中miR-148a的表达水平，探讨miR-148a表达与患者临床病理指标及预后的相关性。 方法收集2009年1至12月在山东大学齐鲁医院胸外科行食管癌切除加系统性淋巴结清扫的75例食管鳞癌患者的肿瘤组织标本，采用实时荧光定量PCR法检测miR-148a的表达。应用SPSS 18.0软件建立数据库并进行统计分析。χ²检验分析miR-148a表达与患者临床病理指标之间的关系；Kaplan-Meier法绘制患者的生存曲线，Log-rank检验比较患者的生存差别，Cox回归多因素分析判定独立的预后因素。 结果有32例患者肿瘤组织中miR-148a为低表达，miR-148a的低表达率为42.7%(32/75)，与肿瘤浸润深度(χ²＝8.149，P＝0.017)、淋巴结转移(χ²＝4.151，P＝0.042)及病理分期(χ²＝6.474，P＝0.039)显著相关。患者术后3年的总生存率为70.7%。单因素生存分析结果显示，miR-148a低表达患者的术后3年总生存率显著低于miR-148a高表达患者(53.1%和83.7%，χ²＝9.136，P＝0.003)。Cox多因素回归分析结果显示，肿瘤浸润深度(95%CI为1.015～2.799，P＝0.044)及淋巴结转移(95%CI为1.285～4.796，P＝0.007)分别是判定患者术后3年总生存率的独立预后因素。 结论miR-148a在食管鳞癌组织中存在异常低表达，并与肿瘤进展及患者的不良预后密切相关；miR-148a可作为预测食管鳞癌进展和判定患者不良预后的参考指标。

Clinical significance of miR-148a expression in patients with esophageal squamous cell cancer

ObjectiveTo detect the expression of miR-148a in the tissues of esophageal squamous cell cancer, and investigate its clinicopathological and prognostic significance. MethodsThe tumor tissue specimens of 75 patients with esophageal squamous cell cancer undergoing subtotal esophagectomy and regional lymph node dissection between January 2009 and December 2009 at Qilu Hospital, Shandong University were obtained. Real-time PCR was performed to detect the expression of miR-148a. All statistical analyses were done with SPSS 18.0 software. χ² test was used to examine the association between miR-148a expression and clinicopathological factors. Survival curves were plotted by the Kaplan-Meier method, and survival differences were compared by the Log-rank test. Cox regression multivariate analysis was conducted to identify significantly independent prognostic factors. ResultsThe low expression of miR-148a was detected in 32(42.7%, 32/75) cases, and significantly correlated with infiltration depth (χ²=8.149, P=0.017), lymph node metastasis (χ²=4.151, P=0.042) and pathological stage (χ²=6.474, P=0.039). The overall 3-year survival after operation was 70.7%, and univariate survival analysis demonstrated that patients with low expression of miR-148a had significantly lower 3-year overall survival than those with high expression of miR-148a (53.1% vs 83.7%, χ²=9.136, P=0.003). Cox regression multivariate survival analysis indicated that infiltration depth (95%CI: 1.015-2.799, P=0.044) and lymph node metastasis (95%CI: 1.285-4.796, P=0.007) were independent predictors for 3-year overall survival. ConclusionsAberrant low expression of miR-148a exists in tissues of esophageal squamous cell cancer, and is significantly associated with tumor progression and unfavorable prognosis. miR-148a may serve as an indicator of progression and poor prognosis of esophageal squamous cell cancer.