Expression Levels of the Uridine-Cytidine Kinase Like-1 Protein As a Novel Prognostic Factor for Hepatitis C VirusAssociated Hepatocellular Carcinomas

Abstract

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.

UCK2 upregulation might serve as an indicator of unfavorable prognosis of hepatocellular carcinoma

“…However, only UCK2, but not UCKL1 was associated with survival outcomes of HCC patients. Although one previous study found that in hepatitis C virusassociated HCC, high UCKL1 expression might be a prognostic factor for disease recurrence, in combination with age and microvascular invasion (12), we failed to confirm these associations in this study. We guess that the discrepancy might be due to different virus infection status between the patients.…”

Development and evaluation of a risk score model based on a WNT score gene-associated signature for predicting the clinical outcome and the tumour microenvironment of hepatocellular carcinoma

“…UCKL1 upregulation, age, and microvascular factors could effectively predict cancer recurrence. 33 Myristoylated alanine-rich C kinase substrate-like protein-1 (MARCKSL1) is a conserved membrane-associated gene regulating cell migration, adhesion, secretion, cell shape, and vessel structure during angiogenesis. 34,35 Zhu et al (2019) 36 reported that MARCKSL1 was highly expressed in patients with HCC and short OS.…”

Expression pattern of MRPS18 family genes in gliomas

“…Only one MRPS18 gene is found in the bacterial genome, while three S18 genes are encoded by the human genome [1]. Earlier, we have shown that the S18-2 protein is expressed at high levels in several tumor tissues, compared to their normal counterpart, such as endometrial [2], breast [3], prostate [4] cancers, hepatocellular carcinomas [5] and in Hodgkin's lymphomas [6]. Moreover, S18-3 is also overexpressed in breast cancer [7] and in Hodgkin's lymphomas [6].…”