👤 Ahmed R Sofy

The molecular pathogenesis of hepatocellular carcinoma (HCC) exhibits striking etiological heterogeneity, with non-HCV-associated cases representing an increasingly prominent clinical challenge in regions like Egypt, where environmental carcinogens significantly contribute to the disease burden. Through integrated analysis of genomic data Egyptian cohort comprising 48 HCC cases (23 non-HCV, 25 HCV-positive) was examined and validated against TCGA/ICGC datasets using cBioPortal and Cytoscape. This study identifies a distinct oncogenic program in non-viral HCC characterized by recurrent alterations in receptor tyrosine kinases (RTKs) FGFR1, MET, ERBB2 and FLT3. These mutations were found to be 4.3-fold more prevalent in non-HCV HCC compared to viral counterparts (26.1% vs. 6.0%, p=0.008), demonstrating strong etiological specificity. Functional characterization revealed these alterations converge on MAPK and PI3K-AKT-mTOR signaling cascades through shared adaptor proteins, creating an interconnected signaling network that drives tumor progression. Clinically, FGFR1/MET co-alterations predicted significantly worse outcomes (HR=2.3 for recurrence, 95% CI 1.1-4.8), while maintaining 92% specificity for non-viral HCC diagnosis. These findings establish the FGFR1-MET-ERBB2 axis as both a molecular classifier and therapeutic target, providing a rationale for etiology-specific management strategies in HCC precision oncology. Show less

Malignant liver disease is among the highest in the world, with hepatocellular carcinoma (HCC) accounting for up to 90 % of all cases. In Egypt, HCC poses a significant public-health concern, representing 47.17 % of cancer cases. The high incidence of hepatitis C virus (HCV) in the Egypt was a major predisposing factor for HCC. This study included 63 Egyptian HCC patients, 55 % of whom had a history of HCV infection. Using a paired sampling strategy, approximately 2800 COSMIC mutations from 50 oncogenes and tumor-suppressor genes were NGS sequenced. Total of 381 somatic mutations were identified, 91 mutations detected in the HCC group and 291 in the HCV-related HCC group. The top 10 mutated genes in the non-HCV group were TP53, ATM, EGFR, CDH1, FGFR1, MET, SMAD4, ERBB2, FLT3, and FBXW7, while in the HCV-related HCC group, genes were KIT, ATM, TP53, APC, FBXW7, KDR, RB1, SMAD4, EGFR, and PIK3CA. The present study represents the first comprehensive somatic mutation profile in HCC Egyptian patients. This finding suggests that HCV viral infection played a direct and indirect role in increasing the somatic mutation burden in HCV-related HCC patients and opens new promises of targeted therapies for those patients. Show less