Acta NaturaeActa NaturaeActa Naturae2075-8251Acta Naturae Ltd1038610.32607/20758251-2017-9-3-108-114Research ArticlesЭкспериментальные статьиResearch ArticleExpression Levels of the Uridine-Cytidine Kinase Like-1 Protein As a Novel Prognostic Factor for Hepatitis C VirusAssociated Hepatocellular CarcinomasExpression Levels of the Uridine-Cytidine Kinase Like-1 Protein As a Novel Prognostic Factor for Hepatitis C VirusAssociated Hepatocellular CarcinomasBuivydieneA.
Lithuania
arida.buivydiene@santa.ltLiakinaV.
Lithuania
arida.buivydiene@santa.ltValantinasJ.
Lithuania
arida.buivydiene@santa.ltNorkunieneJ.
Lithuania
arida.buivydiene@santa.ltMockieneE.
Lithuania
arida.buivydiene@santa.ltJokubauskieneS.
Lithuania
arida.buivydiene@santa.ltSmaliukieneR.
Lithuania
arida.buivydiene@santa.ltJancorieneL.
Lithuania
arida.buivydiene@santa.ltKovalevskaL.
Ukraine
arida.buivydiene@santa.ltKashubaE.
Ukraine
Elena.Kashuba@ki.seVilnius UniversityVilnius Gediminas Technical UniversityVilnius College of Higher EducationCentre of Radiology and Nuclear MedicineNational Center of PathologyNational Center of PathologyVilnius UniversityR.E. Kavetsky Institute of Experimental PathologyKarolinska Institutet1509201793VOL 9, NO3 (2017)ТОМ 9, №3 (2017)10811417012020Copyright ©; 2017, Buivydiene A., Liakina V., Valantinas J., Norkuniene J., Mockiene E., Jokubauskiene S., Smaliukiene R., Jancoriene L., Kovalevska L., Kashuba E.Copyright ©; 2017, Buivydiene A., Liakina V., Valantinas J., Norkuniene J., Mockiene E., Jokubauskiene S., Smaliukiene R., Jancoriene L., Kovalevska L., Kashuba E.2017Buivydiene A., Liakina V., Valantinas J., Norkuniene J., Mockiene E., Jokubauskiene S., Smaliukiene R., Jancoriene L., Kovalevska L., Kashuba E.Buivydiene A., Liakina V., Valantinas J., Norkuniene J., Mockiene E., Jokubauskiene S., Smaliukiene R., Jancoriene L., Kovalevska L., Kashuba E.https://creativecommons.org/licenses/by/4.0https://actanaturae.ru/2075-8251/article/view/10386

The expression levels of the two novel oncoproteins uridine-cytidine kinase like-1 (UCKL-1) and mitochondrial ribosomal protein S18-2 (MRPS18-2) were assessed in samples of hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC) using immunohistochemistry. Tissue microarray (TMA) paraffin blocks were prepared from 42 HCC tumor samples with the corresponding peri-tumor tissues and from 11 tissues of a liver with HCV-induced cirrhosis. We found that the UCKL-1 signal in the liver tissues of the peri-tumor zone in the HCC samples was stronger than that in cirrhosis (50 ± 49.44 vs. 24.27 ± 14.53; p = 0.014). The MRPS18-2 expression was weak, and there was no differences between the groups (p = 0.26). Noteworthy, the UCKL-1 protein was expressed at higher levels in peri-tumor tissues in the cases of HCC recurrence; this was confirmed for 27 older patients (63.78 ± 9.22 vs. 53.53 ± 4.07 years, p < 0.001), in parallel with enhanced UCKL-1 staining in former HCC nodules (62.69 ± 50.4 vs. 26.0 ± 30.19, p = 0.006) and microvascular invasion (p = 0.02). A multivariate analysis of prognostic factors for HCC recurrence showed that the best predictive factors for these conditions were UCKL-1 expression in tumor, vascular invasion, and HCC treatment modality, other than liver transplantation (odds ratios: 1.029, 18.143 and 11.984, R² = 0.633, p = 0.002). In conclusion, the high UCKL-1 expression might be a prognostic factor for HCC relapse, in combination with age and microvascular invasion. MRPS18-2 protein expression has no prognostic significance in the cases of HCV-associated HCC.

The expression levels of the two novel oncoproteins uridine-cytidine kinase like-1 (UCKL-1) and mitochondrial ribosomal protein S18-2 (MRPS18-2) were assessed in samples of hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC) using immunohistochemistry. Tissue microarray (TMA) paraffin blocks were prepared from 42 HCC tumor samples with the corresponding peri-tumor tissues and from 11 tissues of a liver with HCV-induced cirrhosis. We found that the UCKL-1 signal in the liver tissues of the peri-tumor zone in the HCC samples was stronger than that in cirrhosis (50 ± 49.44 vs. 24.27 ± 14.53; p = 0.014). The MRPS18-2 expression was weak, and there was no differences between the groups (p = 0.26). Noteworthy, the UCKL-1 protein was expressed at higher levels in peri-tumor tissues in the cases of HCC recurrence; this was confirmed for 27 older patients (63.78 ± 9.22 vs. 53.53 ± 4.07 years, p < 0.001), in parallel with enhanced UCKL-1 staining in former HCC nodules (62.69 ± 50.4 vs. 26.0 ± 30.19, p = 0.006) and microvascular invasion (p = 0.02). A multivariate analysis of prognostic factors for HCC recurrence showed that the best predictive factors for these conditions were UCKL-1 expression in tumor, vascular invasion, and HCC treatment modality, other than liver transplantation (odds ratios: 1.029, 18.143 and 11.984, R² = 0.633, p = 0.002). In conclusion, the high UCKL-1 expression might be a prognostic factor for HCC relapse, in combination with age and microvascular invasion. MRPS18-2 protein expression has no prognostic significance in the cases of HCV-associated HCC.

hepatitis C virus (HCV)hepatocellular carcinoma (HCC)recurrence of hepatocellular carcinomaUCKL-1MRPS18-2prognostic factorsThis work was supported by the Swedish Cancer Society, matching grants from the Concern Foundation (Los Angeles) and the Cancer Research Institute (New York), the Ministry of Education and Science of Ukraine (No.0116U005456), and the Research Council of Lithuania (No.TAP-LU-15-003).[1] Torre L.A., Bray F., Siegel R.L., Ferlay J., Lortet-Tieulent J., Jemal A. // CA: Cancer JClinicians. 2015, V.65, №2, P.87-108[2] McGlynn K.A., London W.T. // Clinics Liver Disease. 2011, V.15, №2, Ptvii-x, P.223-243[3] El-Serag H.B. // N. Eng. J. Med. 2011, V.365, №12, P.1118-1127[4] Liakina V., Valantinas J. // Med. Sci. Monitor: Internat. Med. J. Exp. Clin. Res. 2012, V.18, №3, P.PH28-PH35[5] Goossens N., Hoshida Y. // Clin. Mol. Hepatol. 2015, V.21, №2, P.105-114[6] van der Meer A.J., Veldt B.J., Feld J.J., Wedemeyer H., Dufour J.F., Lammert F., Duarte-Rojo A., Heathcote E.J., Manns M.P., Kuske L. // JAMA. 2012, V.308, №24, P.2584-2593[7] Bruno S., Crosignani A., Roffi L., De Lisi S., Rossi S., Boccaccio V., Zermiani P., Mondelli V., Maisonneuve P. // J. Hepatol. 2014, V.60, №1, P.S224[8] Davila J.A., Morgan R.O., Richardson P.A., Du X.L., McGlynn K.A., El-Serag H.B. // Hepatology. 2010, V.52, №1, P.132-141[9] Hoshida Y., Fuchs B.C., Bardeesy N., Baumert T.F., Chung R.T. // J. Hepatol. 2014, V.61, №1, P.79-90[10] Waghray A., Murali A.R., Menon K.V.N. // W.J. Hepatol. 2015, V.7, №8, P.1020-1029[11] Colecchia A., Schiumerini R., Cucchetti A., Cescon M., Taddia M., Marasco G., Festi G. // World J. Gastroenterol. 2014, V.20, №20, P.5935-5950[12] Smirnova I.S., Aksenov N.D., Kashuba E.V., Payakurel P., Grabovetsky V.V., Zaberezhny A.D., Vonsky M.S., Buchinska L., Biberfeld P., Hinkula J. // Oncol.: Official J. Internat. Soc. Cell. Oncol. // Cell. 2006, V.28, №4, P.177-190[13] Darekar S.D., Mushtaq M., Gurrapu S., Kovalevska L., Drummond C., Petruchek M., Tirinato L., Di Fabrizio E., Carbone E., Kashuba E. // Oncotarget. 2015, V.6, №25, P.21016-21028[14] Ambrose E.C., Kornbluth J. // Apoptosis: Internat. J. Programmed Cell Death. 2009, V.14, №10, P.1227-1236[15] Kashuba E., Kashuba V., Sandalova T., Klein G., Szekely L. // BMC Cell Biol. 2002, V.3, №1, P.1-12[16] Kashuba E., Pavan Yenamandra S., Darekar S.D., Yurchenko M., Kashuba V., Klein G., Szekely L. // Proc. Natl. Acad. Sci. USA. 2009, V.106, №47, P.19866-19871[17] Shevchuk Z., Yurchenko M.Y., Darekar S.D., Holodnuka-Kholodnyuk I., Kashuba V.I., Kashuba E.V. // Acta Naturae. 2013, V.5, №1, P.85-89[18] Ishak K., Baptista A., Bianchi L., Callea F., De Groote J., Gudat F., Denk H., Desmet V., Korb G., MacSween R.N.M. // J. Hepatol. 1995, V.22, №6, P.696-699[19] Bedossa P., Poynard T. // Hepatology. 1996, V.24, №2, P.289-293[20] Goodman Z.D. // J. Hepatol. 2007, V.47, №4, P.598-607[21] Llovet J.M., Burroughs A., Bruix J. // Lancet. 2003, V.362, №9399, P.1907-1917[22] El-Serag H.B., Rudolph K.L. // Gastroenterology. 2007, V.132, №7, P.2557-2576[23] Lauwers G.Y., Terris B., Balis U.J., Batts K.P., Regimbeau J.M., Chang Y., Graeme-Cook F., Yamabe H., Ikai I., Cleary K.R. // Am. J. Surgical Pathol. 2002, V.26, №1, P.25-34[24] Wahab M.A., Shehta A., Hamed H., El Nakeeb A., Salah T. // Eurasian J. Med. 2014, V.46, №1, P.36-41[25] Llovet J.M., Schwartz M., Mazzaferro V. // Semin. Liver Dis. 2005, V.25, №2, P.181-200[26] Welker M.W., Bechstein W.O., Zeuzem S., Trojan J. // Transplant Internat. 2013, V.26, №2, P.109-118[27] Lim K.C., Chow P.K., Allen J.C., Siddiqui F.J., Chan E.S., Tan S.B. // Br. J. Surgery. 2012, V.99, №12, P.1622-1629