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微小RNA-224的表达及多态性可预测乙型肝炎病毒相关肝细胞癌患者肝切除术后的预后

MicroRNA-224 Expression and Polymorphism Predict the Prognosis of Hepatitis B Virus-Related Hepatocellular Carcinoma Patients After Liver Resection.

作者信息

Wu Chaoyu, Wang Xiaoying, Zhang Jian, Tang Gongen, Xu Yanmei, Lu Cuihong, Li Yun

出版信息

Clin Lab. 2019 Jun 1;65(6). doi: 10.7754/Clin.Lab.2018.181025.

DOI:10.7754/Clin.Lab.2018.181025
PMID:31232017
Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) is one of the common lethal types of tumors all over the world. Overexpression of mircoRNA-224 (miR-224) has been reported to act as a potential biomarker for HCC patients. The goal of our study was to assess the prognostic impact of the expression and polymorphism of miR-224 in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients after liver resection.

METHODS

A total of 62 cases of HBV-positive HCC patients, 17 HCC patients without HBV, and 13 healthy cases were enrolled in this study. Blood leukocyte miR-224 level were determined by qRT-PCR. Genotyping analysis of miR-224 rs188519172 was performed using an allele-specific PCR assay. All patients were undergoing partial liver resection and the prognostic values of miR-224 rs188519172 polymorphism for tumor development, survival rate, and liver injury after liver resection were examined.

RESULTS

When we compared the blood leukocyte miR-224 level between HCC patients and healthy cases, we found that it was significantly increased in HCC patients. By subgroup analysis, it demonstrated that miR-224 expression was significantly increased in the HBV positive group compared with the HBV negative group. miR-224 rs188519172 AG + GG phenotype was significantly associated with severe liver injury after liver resection and patients carrying miR-224 rs188519172 AG + GG phenotype have a higher risk of cirrhosis and lower overall and disease-free survival rate. Meanwhile, the combination of miR-224 rs188519172 AG + GG phenotype and AFP value could improve the prognosis assessment of HBV related HCC.

CONCLUSIONS

miR-224 rs188519172 polymorphism is an indicator of liver injury and a novel prognostic biomarker for tumor development and survival of HBV related HCC patients after liver resection.

摘要

背景

肝细胞癌(HCC)是全球常见的致命性肿瘤类型之一。据报道,微小RNA-224(miR-224)的过表达可作为HCC患者的潜在生物标志物。我们研究的目的是评估miR-224的表达及多态性对乙型肝炎病毒(HBV)相关肝细胞癌(HCC)患者肝切除术后预后的影响。

方法

本研究共纳入62例HBV阳性HCC患者、17例无HBV的HCC患者和13例健康对照。采用qRT-PCR检测血液白细胞中miR-224水平。使用等位基因特异性PCR法对miR-224 rs188519172进行基因分型分析。所有患者均接受肝部分切除术,并检测miR-224 rs188519172多态性对肝切除术后肿瘤发展、生存率和肝损伤的预后价值。

结果

比较HCC患者与健康对照的血液白细胞miR-224水平时,我们发现HCC患者中该水平显著升高。亚组分析表明,与HBV阴性组相比,HBV阳性组中miR-224表达显著升高。miR-224 rs188519172 AG + GG基因型与肝切除术后严重肝损伤显著相关,携带miR-224 rs188519172 AG + GG基因型的患者发生肝硬化的风险更高,总生存率和无病生存率更低。同时,miR-224 rs188519172 AG + GG基因型与甲胎蛋白(AFP)值的联合检测可改善对HBV相关HCC的预后评估。

结论

miR-224 rs188519172多态性是肝损伤的一个指标,也是HBV相关HCC患者肝切除术后肿瘤发展和生存的一种新型预后生物标志物。

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