Does Beclin-1 have a role in hepatocellular carcinoma in Egyptian patients?

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Abstract

Background and aim

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and it constitutes 78.64% of all liver tumors among Egyptians. Autophagy is a genetically regulated process that enables the turnover of long-lived proteins or damaged cellular organelles. It has two faces as it may stimulate cell survival by suppression of apoptosis or stimulate cell death by triggering apoptosis. The B-cell lymphoma (Bcl-2)/Beclin-1 interaction is a very important checkpoint in the regulation of autophagy and can therefore be regulated by a number of molecules. Many important questions regarding this interaction still remain to be investigated; further, the role of autophagy in carcinogenesis, either oncogenic or tumor suppressor, is still controversial. The aim of this work was to evaluate the role of Beclin-1 and Bcl-2 in HCC in Egyptian patients.

Materials and methods

This is a retrospective study that included 69 liver specimens retrieved from the archival material of the Pathology Department, National Liver Institute, Menoufia University, Egypt, spanning the period between March 2007 and October 2014. The specimens consisted of 54 HCC and 15 cirrhotic cases. All cases were stained for Beclin-1 and Bcl-2 antibodies.

Results

Ninety-six percent of the studied HCC cases and all cirrhotic cases showed positive Beclin-1 expression. In contrast, all HCC and cirrhotic cases were negative for Bcl-2 immunostaining. There was a statistically significant association between low Beclin-1 expression and multiple tumor focality (P=0.039), advanced stage (P=0.000), and presence of lymphovascular invasion (P=0.000). There was a statistically significant association between high Beclin-1 expression and smaller regeneration nodules (≤5 cm) (P=0.028) in cirrhotic cases. Furthermore, there was no significant association between HCC and cirrhotic cases regarding Beclin-1-positive expression. Moreover, there was no statistically significant association between Beclin-1-positive expression and hepatitis c virus-associated HCC and cirrhotic cases.

Conclusion

Beclin-1 is a good prognostic marker in view of the association between low Beclin-1 expression and high lymphovascular invasion and advanced pathological stage. Moreover, there is a reciprocal talk between Beclin-1 and Bcl-2, as under stressful conditions (HCC or cirrhosis) Beclin-1 dissociated from the Beclin-1–Bcl-2 complex, modulating the tumor suppressor action of Beclin-1.

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