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Open Access Highly Accessed Research article

Autophagy and apoptosis-related genes in chronic liver disease and hepatocellular carcinoma

Andromachi Kotsafti, Fabio Farinati, Romilda Cardin, Umberto Cillo, Donato Nitti and Marina Bortolami*

Author Affiliations

Department of Surgery, Oncology and Gastroenterology Division of Gastroenterology, University of Padova Via Giustiniani 2, 35128, Padova, Italy

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BMC Gastroenterology 2012, 12:118  doi:10.1186/1471-230X-12-118

Published: 28 August 2012

Abstract

Background

Dysregulation of autophagy is important in the pathogenesis of many diseases, including cancer. Several aspects of the biological role of autophagy are however still unclear and the relationship between apoptosis and autophagy, particularly in the liver has yet to be thoroughly explored. In this study we evaluated the expression of Beclin 1 (one of the main autophagocytic agents, which bridges autophagy, apoptosis and both differentiation), and both pro- (Bad, Bax) and anti-apoptotic (Bcl-2, Bcl-xL) factors in liver samples from patients with different stages of liver disease.

Methods

The study concerned 93 patients from 49 cases of chronic hepatitis (CH) (30 HCV and 19 HBV-related), 13 of cirrhosis (CIRR) (10 HCV and 3 HBV-related), 21 of hepatocellular carcinoma (both HCC and peritumoral tissues [PHCC]), and 10 controls (CONTR). Real-time PCR and Western blotting were used to measure mRNA and protein expression levels.

Results

Beclin 1 mRNA levels were lower in HCC than in CH (P = 0.010) or CIRR (P = 0.011), and so were the Bcl-xL transcripts (P < 0.0001). Bad mRNA levels were higher in CH and CIRR than in CONTR, while Bax transcripts were increased in all tissues (P = 0.036). PHCC expressed the highest Bcl-2 mRNA levels. HBV-related CH tissues showed significantly higher Bcl-xL and Bad mRNA levels than HCV-related CH (P = 0.003 and P = 0.016, respectively).

Conclusions

High Beclin 1, Bcl-xL and Bad levels in CH and CIRR tissues suggest an interaction between autophagy and apoptosis in the early and intermediate stages of viral hepatitis. In HCC these processes seem to be downregulated, probably enabling the survival and growth of neoplastic hepatocytes.

Keywords:
Autophagy; B and C virus infection; Beclin 1; Hepatocellular carcinoma; Pro- and anti-apoptotic factors.