Krupa Renata, Malecki Wojciech, Czarny Piotr, Strycharz Justyna, Jablkowski Maciej, Kordek Radzislaw, Szemraj Janusz, Sliwinski Tomasz
Laboratory of Medical Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.
Department of Infectious and Liver Disease, Medical University of Lodz, Lodz, Poland.
Arch Med Sci. 2019 Jul 12;17(5):1175-1183. doi: 10.5114/aoms.2019.86613. eCollection 2021.
Hepatocellular carcinoma (HCC) is very difficult to diagnose, especially in its early stages. Non-invasive diagnostic and prognostic factors for this cancer are urgently needed. The purpose of our study was to investigate whether the microRNAs (miRNAs) regulating genes involved in iron homeostasis, whose disruption is a hallmark of HCC, offer potential as diagnostic or prognostic factors of HCV-related hepatocellular carcinoma.
Serum and tumor samples, and adjacent liver specimens, were obtained from 65 HCC patients. Additionally, serum samples were obtained from 65 healthy controls. In total, 28 circulating and eight tissue microRNA expression profiles were estimated by TaqMan qPCR.
The expression profiles of all tested miRNAs were altered in the hepatocellular carcinoma patients. Iron level was negatively related to serum miR-96 level in healthy controls. Although the expression of iron metabolism proteins correlated with the level of serum miRNA in the controls, this was not observed in cancer patients. In the group of cancer patients, Let-7a, miR-29b, and miR-133a were positively related to ferroportin, transferrin and ferritin levels, while miR-31, miR-221 and miR-532 were negatively related to ferroportin, transferrin receptor 1 and ferritin levels. According to ROC curve analyses, 15 miRNAs are able to discriminate with 100% sensitivity and specificity between hepatocellular carcinoma patients and healthy subjects, which is more efficient than α-fetoprotein.
Circulating miRNAs that regulate the expression of iron metabolism proteins should be evaluated as promising candidates for HCV-related HCC diagnostic agents.
肝细胞癌（HCC）很难诊断，尤其是在早期阶段。迫切需要针对这种癌症的非侵入性诊断和预后因素。我们研究的目的是调查调节铁稳态相关基因的微小RNA（miRNA）是否具有作为丙型肝炎病毒（HCV）相关肝细胞癌诊断或预后因素的潜力，铁稳态破坏是HCC的一个标志。
从65例HCC患者中获取血清和肿瘤样本以及相邻肝脏标本。此外，从65名健康对照者中获取血清样本。总共通过TaqMan定量聚合酶链反应（qPCR）评估了28种循环和8种组织微小RNA表达谱。
所有检测的miRNA的表达谱在肝细胞癌患者中均发生改变。在健康对照者中，铁水平与血清miR - 96水平呈负相关。虽然在对照者中铁代谢蛋白的表达与血清miRNA水平相关，但在癌症患者中未观察到这种情况。在癌症患者组中，Let - 7a、miR - 29b和miR - 133a与铁转运蛋白、转铁蛋白和铁蛋白水平呈正相关，而miR - 31、miR - 221和miR - 532与铁转运蛋白、转铁蛋白受体1和铁蛋白水平呈负相关。根据受试者工作特征（ROC）曲线分析，15种miRNA能够以100%的灵敏度和特异性区分肝细胞癌患者和健康受试者，这比甲胎蛋白更有效。
调节铁代谢蛋白表达的循环miRNA应被评估为HCV相关HCC诊断试剂的有前景的候选物。
