Expression signature of lysosomal-associated transmembrane protein 4B in hepatitis C virus-induced hepatocellular carcinoma.

Abstract

Hepatocellular carcinoma is a lethal disease worldwide and therefore the establishment of novel diagnostic biomarkers is imperative. In this study, it was hypothesized that an abnormal expression of the lysosomal-associated protein transmembrane 4 beta ( LAPTM4B) gene is crucial in the pathogenesis of hepatitis C virus-mediated hepatocellular carcinoma; hence we investigated the expression profile of LAPTM4B in hepatitis C virus-induced hepatocellular carcinoma. A group of 189 consecutive patients (hepatitis C virus-related hepatocellular carcinoma as tumor cases; n=93, hepatitis C virus-related cirrhotics as disease controls; n=96) opting for living donor liver transplantation as a therapeutic surgical regimen were recruited with informed consent. Additionally, paired adjacent non-tumorous tissues (n=93) obtained from cases were also included. Serum LAPTM4B protein concentrations were assessed by third-generation enzyme-linked immunosorbent assay and LAPTM4B mRNA, and protein expressions at tissue level were determined by quantitative real time reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry techniques, respectively. LAPTM4B protein concentrations in sera of patients were higher ( p<0.001) in tumor cases (1.25±0.25 ng/ml) compared to disease controls (0.53±0.28 ng/ml). Our study also depicts positive clinicopathological correlations between alpha-fetoprotein titers (b=0.65; p<0.001), quantitative hepatitis C virus RNA copies (b=0.33; p<0.001), and LAPTM4B protein concentrations, all in sera of patients. In addition, qRT-PCR and immunohistochemistry analyses revealed a significantly higher ( p<0.05) tissue LAPTM4B mRNA and protein expression, respectively, in tumor cases rather than in non-tumorous tissues and disease controls. Together, our results illustrate the LAPTM4B gene as a diagnostic biomarker in patients with hepatocellular carcinoma having documented evidence of chronic hepatitis C virus infection.