Published September 27, 2018 | Version v1
Journal article Open

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

  • 1. Center of Hepatology, Gastroenterology and Dietetics, Clinic of Gastroenterology, Nephrourology and Surgery, Vilnius University, LT-08661 Vilnius, Lithuania
  • 2. Center of Hepatology, Gastroenterology and Dietetics, Clinic of Gastroenterology, Nephrourology and Surgery, Vilnius University, LT-08661 Vilnius, Lithuania; Department of Chemistry and Bioengineering, Faculty of Fundamental Sciences, Vilnius Gediminas Technical University, LT-10223 Vilnius, Lithuania
  • 3. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden; RE Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, UA-03022 Kyiv, Ukraine
  • 4. Department of Mathematical Statistics, Faculty of Fundamental Sciences, Vilnius Gediminas Technical University, LT-10223 Vilnius, Lithuania; Vilniaus Kolegija/University of Applied Sciences, LT-08105 Vilnius, Lithuania
  • 5. Department of Pathology, Forensic Medicine and Pharmacology, Faculty of Medicine, Vilnius University, LT-03101 Vilnius, Lithuanian; National Center of Pathology, LT-08406 Vilnius, Lithuania
  • 6. Center of Hematology, Oncology and Transfusion Medicine, Vilnius University Hospital Santaros Klinikos, LT-08661 Vilnius, Lithuania; Life Sciences Center, Vilnius University, LT-10257 Vilnius, Lithuania

Description

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. 

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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.pdf