Impact of the Uridine⁻Cytidine Kinase Like-1 Protein and IL28B rs12979860 and rs8099917 SNPs on the Development of Hepatocellular Carcinoma in Cirrhotic Chronic Hepatitis C Patients-A Pilot Study.

Arida Buivydiene,Jonas Valantinas,Jolita Norkuniene,Skirmante Jokubauskiene,Elena Kashuba,Egle Gineikiene,Valentina Liakina

doi:10.3390/medicina54050067

Abstract

Background and objectives: The hepatitis C virus (HCV) is the major causative agent of hepatocellular carcinoma (HCC) in the western world. The efficacy of surveillance programs for early detection of HCC is not satisfactory: many tumors are diagnosed at the late, incurable stages. Therefore, there is a need in reliable prognostic markers for the proper follow-up of HCV-positive patients. The aim of the present study was to assess the prognostic value of the uridine–cytidine kinase-like protein 1 (UCKL-1), a putative oncoprotein, together with genetically determined polymorphisms in the interleukin 28B (IL28B) gene (rs12979860, rs8099917) in the development of HCC in HCV-positive cirrhotic patients. Materials and Methods: We included 32 HCV cirrhotic patients, 21 (65.6%) of whom had HCC. The expression of UCKL-1 was assessed in liver tissue sections, using immunohistochemistry. For IL28B rs12979860 and rs8099917 genotype analysis, the corresponding genomic regions were amplified by polymerase chain reaction (PCR) with appropriate primers. Results: We have found that UCKL-1 expression was significantly increased in HCC (p = 0.003). The presence of rs8099917 TT single-nucleotide polymorphism (SNP) elevated the chances of HCC manifestation more than sevenfold (OR = 7.3, p = 0.0273). The presence of rs12979860 CC SNP also heightened HCC chances more than sevenfold (OR = 7.5, p = 0.0765). Moreover, in the HCC group, a combination of IL28B rs12979860 non-TT and rs8099917 TT genotypes was observed more often, compared with the non-HCC group. Other combinations of IL28B rs12979860 and rs8099917 SNIPs were associated with a reduced risk of HCC development, approximately at the same extent. Conclusions: The presence of IL28B rs8099917 TT and rs12979860 CC SNPs, but not the intensity of UCKL-1 expression, is strongly associated with increased chances of HCC development in HCV-positive cirrhotic patients.

Highlights

The burden of mortality due to liver cancer is in second place after lung cancer worldwide [1].Hepatocellular carcinoma (HCC) represents more than 90% of primary liver cancers [2]
Most patients in the non-hepatocellular carcinoma (HCC) group were of 40–50 years old, while they patients were somewhat older (50–60 years old) in the HCC group
The hepatitis C virus (HCV) genotypes did not differ in HCC and non-HCC groups (p = 0.307)

Summary

Introduction

The burden of mortality due to liver cancer is in second place after lung cancer worldwide [1].Hepatocellular carcinoma (HCC) represents more than 90% of primary liver cancers [2]. A major risk factor for HCC development is liver cirrhosis; about 80–90% of detected HCC cases are found in cirrhotic liver [3]. HCC is usually diagnosed at the late incurable stages or during surveillance for HCC in cirrhosis using ultrasound examination every six months, according to the guidelines from the European Association for the. There is a need in reliable prognostic markers for the proper follow-up of HCV-positive patients. The aim of the present study was to assess the prognostic value of the uridine–cytidine kinase-like protein 1 (UCKL-1), a putative oncoprotein, together with genetically determined polymorphisms in the interleukin 28B (IL28B) gene (rs12979860, rs8099917) in the development of HCC in HCV-positive cirrhotic patients. The expression of UCKL-1 was assessed in liver tissue sections, using immunohistochemistry.

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Discussion

Conclusion