Mitochondrial DNA Copy Number in Egyptian Patients with Hepatitis C Virus-Related Hepatocellular Carcinoma

Mitochondrial DNA Copy Number in Egyptian Patients with Hepatitis C Virus-Related Hepatocellular Carcinoma
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DOI:
10.1089/gtmb.2015.0132
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发表时间:
2015-11-01
影响因子:
1.4
通讯作者:
Salem, Perihan E.
Salem, Perihan E.
中科院分区:
生物学4区
文献类型:
--
作者:
Hashad, Doaa I.;Elyamany, Amany S.;Salem, Perihan E.

文献摘要

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目的:评估线粒体 DNA (mtDNA) 含量作为丙型肝炎病毒相关肝细胞癌 (HCV-HCC) 的非侵入性分子生物标志物的用途。材料和方法:共有 135 名参与者参加了该研究。临床定义的三个组中每组均招募了相同数量的受试者:HCV 相关肝硬化(HCV-肝硬化)组、HCV-HCC 组以及年龄和性别匹配且无肝病证据的健康志愿者对照组。使用定量实时聚合酶链反应(PCR)技术测定线粒体DNA浓度。结果:HCV-HCC病例中mtDNA含量最低。 HCV-肝硬化组和对照组之间mtDNA水平没有观察到统计学上的显着差异。具有多中心肝脏病变的 HCC 患者的 mtDNA 含量显着低于疾病进展较轻的 HCC 患者。当使用受试者工作特征曲线分析时,mtDNA 含量的截止值被指定为 34,以区分尚未并发恶性肿瘤的 HCV-HCC 和 HCV-肝硬化患者。当使用健康对照和 HCV 肝硬化组之一或两者作为参考时,较低的 mtDNA 含量与 HCC 风险相关。结论:mtDNA 含量分析可以作为反映 HCV-HCC 病例肿瘤负荷的非侵入性分子生物标志物,并可作为 HCV-肝硬化患者 HCC 风险的预测因子。此外,HCV肝硬化患者和健康对照者之间mtDNA水平的无显着差异可以消除某些肝硬化患者因使用甲胎蛋白而产生的灰色地带。
Aim: To assess the use of mitochondrial DNA (mtDNA) content as a noninvasive molecular biomarker in hepatitis C virus-related hepatocellular carcinoma (HCV-HCC). Materials and Methods: A total of 135 participants were enrolled in the study. Equal numbers of subjects were enrolled in each of three clinically defined groups: those with HCV-related cirrhosis (HCV-cirrhosis), those with HCV-HCC, and a control group of age- and sex-matched healthy volunteers with no evidence of liver disease. mtDNA concentrations were determined using a quantitative real-time polymerase chain reaction (PCR) technique. Results: mtDNA content was lowest among the HCV-HCC cases. No statistically significant difference was observed between the group of HCV-cirrhosis and the control group as regards mtDNA level. HCC patients with multicentric hepatic lesions had significantly lower mtDNA content than HCC patients with less advanced disease. When a receiver operating characteristic curve analysis was used, a cutoff of 34 was assigned for mtDNA content to distinguish between HCV-HCC and HCV-cirrhosis patients who are not yet complicated by malignancy. Lower mtDNA content was associated with HCC risk when using either or both healthy controls and HCV-cirrhosis groups for reference. Conclusions: mtDNA content analysis could serve as a noninvasive molecular biomarker that reflects tumor burden in HCV-HCC cases and could be used as a predictor of HCC risk in patients of HCV-cirrhosis. In addition, the nonsignificant difference of mtDNA level between HCV-cirrhosis patients and healthy controls could eliminate the gray zone created by the use of alpha-fetoprotein in some cirrhotic patients.