Altered Protein and Gene Expression of Beclin-1 Correlates with Poor Prognosis of Hcv-Associated Hepatocellular Carcinoma in Egyptian Patients.

Nermine Ehsan,Maha Elsabaawy,Asmaa Mosbeh,Sally Elkhadry,Asmaa Gomaa,Dina Elazab

doi:10.31557/apjcp.2021.22.4.1115

Abstract

Autophagy modulation has recently been addressed as a novel target for overcoming therapeutic resistance in hepatocellular carcinoma (HCC) to currently available anti-HCC therapy. The aim of this study was to investigate the protein and gene expression of Beclin-1 and its correlation with prognosis in HCV-associated HCC in Egyptian patients. This prospective study included 50 patients with HCV-associated-HCC, treated with surgical resection. Immunohistochemistry of antibody and quantitative real-time PCR of Beclin-1 gene were assessed in liver tissues of HCC. A normal-like expression pattern of Beclin-1 was found in 100% of adjacent liver tissues, while in HCC three various patterns were recognized: negative expression [18 (36%)], over expression [16 (32%)] and normal pattern [16 (32%)] (p=0.001). Beclin-1 mRNA in HCC tissues correlated with protein expression with correlation coefficient of 0.774 (p<0.001). Patients with negative expression of Beclin-1 had a significantly poor overall survival rates compared with patients with normal-like expression pattern (P<0.007), which was confirmed by multivariate analysis (p=0.01). Over-expression of Beclin-1 was significantly associated with vascular invasion (P<0.003). However, high tumor histological grade, focal lesion multiplicity, presence of involved margin or cirrhosis were insignificantly related to Becin-1. Beclin-1 altered expression has an important role in development and prognosis of HCC.

Highlights

Hepatocellular carcinoma (HCC), a global health problem, is the second leading cause of cancer related mortality as reviewed by Gomaa and Waked (Gomaa et al, 2017)
A normal-like expression pattern of Beclin-1 was found in 100% of adjacent liver tissues, while in hepatocellular carcinoma (HCC) three various patterns were recognized: negative expression [18 (36%)], over expression [16 (32%)] and normal pattern [16 (32%)] (p=0.001)
Patients with negative expression of Beclin-1 had a significantly poor overall survival rates compared with patients with normal-like expression pattern (P

Summary

Introduction

Hepatocellular carcinoma (HCC), a global health problem, is the second leading cause of cancer related mortality as reviewed by Gomaa and Waked (Gomaa et al, 2017). Despite advancement in diagnostic and therapeutic modalities, most HCC patients are diagnosed at an advanced tumor stage and are associated with poor prognosis (Kudo, 2017). Histological and molecular factors (Ferrín et al, 2015) have been reported to be associated with the prognosis of HCC, more effective biomarkers are necessary to predict the clinical outcome of patients with HCC (Scaggiante et al, 2014). Autophagy is a non-apoptotic form of programmed cell death as a catabolic response of cells to stress. This process allows cells to maintain homeostasis and recycling intracellular constituents. Stimulation of autophagy may lead to cell death through unknown mechanisms. An alternative non-apoptotic programmed cell death mechanism, “autophagic cell death” was proposed (Madrigal-Matute and Cuervo, 2016)

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