miR-221高表达是肝内胆管细胞癌患者预后不良指标

High expression of miR-221 indicates poor prognosis in patients with intrahepatic cholangiocarcinoma

目的观察miRNAs在肝内胆管细胞癌(ICC)组织中的表达情况,探讨其在患者生存预后中的价值。方法本研究组织标本来源于2000年4月至2014年9月中山大学肿瘤防治中心行手术切除的134例ICC和混合型肝癌(cHCC-CC)患者。收集5例正常胆管组织作为对照。采用qRT-PCR检测miR-221、miR-675、miR-1248和miR-1292在肿瘤组织中的表达水平,并分析其临床病理特征。患者均签署知情同意书,符合医学伦理学规定。相关性分析采用χ^2检验。生存分析采用Kaplan-Meier法和Log-rank检验。对可能影响预后的因素进行单因素及多因素Cox分析。结果134例患者中ICC占63.4%(85/134),cHCC-CC占36.6%(49/134)。肿瘤组织miR-221、miR-675、miR-1248和miR-1292高表达患者分别为43.3%、44.0%、77.6%和59.7%,其中miR-221表达水平与肿瘤淋巴结转移相关,且高表达患者淋巴转移率高(χ^2=7.65,P<0.05)。Cox多因素分析显示,miR-221高表达是患者总体生存的独立危险因素(HR=1.878,95%CI:1.135~3.106;P<0.05)。miR-221高表达患者中位总体生存时间为14.5个月,低表达者34.0个月,高表达患者预后更差(χ^2=8.87,P<0.05)。结论miR-221高表达为ICC患者预后独立危险因素,提示患者生存预后较差。

Objective To observe the expression profile of miRNAs in intrahepatic cholangiocarcinoma(ICC),and to explore its value in predicting the survival and prognosis of ICC patients.Methods The tissue specimens were obtained from 134 patients with ICC or with combined hepatocellular and cholangiocarcinoma(cHCC-CC)receiving surgical resection in Sun Yat-sen University Cancer Center from April 2000 to September 2014.Normal bile duct tissues were collected from 5 patients as controls.The expression levels of miR-221,miR-675,miR-1248 and miR-1292 in tumor tissues were quantitatively detected by qRT-PCR and the clinicopathological characteristics were analyzed.The informed consents of all patients were obtained and the local ethical committee approval was received.Correlation analysis was performed by Chi-square test.Survival analysis was performed by using Kaplan-Meier method and Log-rank test.Factors that may affect the prognosis were subject to univariate and multivariate analyses using Cox's proportional hazard model.Results Among 134 patients,ICC patients accounted for 63.4%(85/134)and cHCC-CC patients 36.6%(49/134).The proportion of patients with high expression of miR-221,miR-675,miR-1248 and miR-1292 in tumor tissues were 43.3%,44.0%,77.6%and 59.7%,respectively.The expression level of miR-221 was significantly correlated with the metastasis of tumor lymph node,and patients with high expression presented with a high incidence of lymph node metastasis(χ^2=7.65,P<0.05).Multivariate analysis demonstrated that high expression of miR-221 was an independent risk factor for the overall survival of patients(HR=1.878,95%CI:1.135-3.106;P<0.05).The median overall survival time of patients with high expression of miR-221 was 14.5 months and 34.0 months for those with low expression of miR-221.The prognosis was worse for patients with high expression(χ^2=8.87,P<0.05).Conclusions High expression of miR-221 is an independent risk factor for clinical prognosis of ICC patients,indicating a poor prognosis in ICC patients.