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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(χ~2=8.149,P=0.017)、淋巴结转移(χ~2=4.151,P=0.042)及病理分期(χ~2=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%,χ~2=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。
Objective To detect the expression of miR-148a in esophageal squamous cell carcinoma and to investigate the correlation between the expression of miR-148a and clinicopathological features and prognosis of esophageal squamous cell carcinoma. Methods Tumor tissue samples from 75 patients with esophageal squamous cell carcinoma who underwent esophagectomy plus systemic lymph node dissection in the Department of Thoracic Surgery, Qilu Hospital of Shandong University from January to December 2009 were collected. The expression of miR-148a was detected by real-time fluorescence quantitative PCR. Application of SPSS 18.0 software to establish a database and statistical analysis. Chi-square test was used to analyze the relationship between the expression of miR-148a and the clinicopathological parameters of patients. Kaplan-Meier method was used to draw the survival curves of patients. Log-rank test was used to compare the survival differences and Cox regression multivariate analysis to determine the independent prognostic factors. Results Low expression of miR-148a and low miR-148a expression were found in 32 of 32 patients (42.7%, 32/75), which were correlated with tumor invasion depth (χ ~ 2 = 8.149, P = 0.017), lymph node metastasis χ ~ 2 = 4.151, P = 0.042) and pathological stage (χ ~ 2 = 6.474, P = 0.039). The 3-year overall survival of patients was 70.7%. The results of univariate survival analysis showed that the overall 3-year survival rate of patients with low expression of miR-148a was significantly lower than that of patients with high miR-148a expression (53.1% vs 83.7%, χ ~ 2 = 9.136, P = 0.003). Cox multivariate regression analysis showed that the depth of invasion (95% CI 1.015 ~ 2.799, P = 0.044) and lymph node metastasis (95% CI 1.285 ~ 4.796, P = 0.007) Rate of independent prognostic factors. Conclusions miR-148a is abnormally low expressed in esophageal squamous cell carcinoma and is closely related to tumor progression and poor prognosis. MiR-148a may serve as a reference index for predicting the progression of esophageal squamous cell carcinoma and determining the prognosis of patients with esophageal squamous cell carcinoma.