MicroRNA profile and iron-related gene expression in hepatitis C-related hepatocellular carcinoma: a preliminary study

Renata Krupa; Wojciech Malecki; Piotr Czarny; Justyna Strycharz; Maciej Jablkowski; Radzislaw Kordek; Janusz Szemraj; Tomasz Sliwinski

doi:10.5114/aoms.2019.86613

MicroRNA profile and iron-related gene expression in hepatitis C-related hepatocellular carcinoma: a preliminary study

Arch Med Sci. 2019 Jul 12;17(5):1175-1183. doi: 10.5114/aoms.2019.86613. eCollection 2021.

Authors

Renata Krupa¹, Wojciech Malecki², Piotr Czarny³, Justyna Strycharz³, Maciej Jablkowski², Radzislaw Kordek⁴, Janusz Szemraj³, Tomasz Sliwinski¹

Affiliations

¹ Laboratory of Medical Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.
² Department of Infectious and Liver Disease, Medical University of Lodz, Lodz, Poland.
³ Department of Medical Biochemistry, Medical University of Lodz, Lodz, Poland.
⁴ Department of Pathology, Medical University of Lodz, Lodz, Poland.

Abstract

Introduction: 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.

Material and methods: 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.

Results: 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.

Conclusions: Circulating miRNAs that regulate the expression of iron metabolism proteins should be evaluated as promising candidates for HCV-related HCC diagnostic agents.

Keywords: hepatitis C virus; hepatocellular carcinoma; iron; iron metabolism; microRNA expression.