Characterization of lncRNA-Driven Networks in Portal Vein Tumor Thrombosis: Implications for Hepatocellular Carcinoma Progression

Abstract

Background: Portal vein tumor thrombosis (PVTT) is a frequent and serious complication of advanced hepatocellular carcinoma (HCC) that often results in poor prognosis. Although PVTT holds significant clinical relevance, the molecular mechanisms driving its formation are not well understood. Long non-coding RNAs (lncRNAs) have emerged as potential contributors to PVTT progression, prompting this study to explore lncRNAs as potential biomarkers for PVTT. Methods: We analyzed publicly available datasets from the Gene Expression Omnibus to identify differentially expressed lncRNAs and mRNAs across three comparisons: normal vs. HCC, normal vs. PVTT, and HCC vs. PVTT. Transcriptional profiles were characterized, and proteins interacting with HCC- and PVTT-specific lncRNAs were screened using online databases, revealing that all interacting proteins were transcription factors (TFs). We constructed lncRNA-TF-target gene regulatory networks by intersecting TF target genes with differentially expressed genes (DEGs) from each comparison. Protein-protein interaction (PPI) network analysis was performed to identify key clusters and hub genes, with TFs such as AR and ESR1 being highlighted. Gene Ontology analyses were conducted to understand the biological functions of the regulatory networks. Results: The study identified distinct transcriptional profiles for normal, HCC, and PVTT samples. Key regulatory networks, involving lncRNAs, TFs, and target genes, were constructed, and significant hub genes, including AR and ESR1, were identified as potential therapeutic targets. PPI network analysis revealed important clusters associated with PVTT progression, while Gene Ontology analyses provided insights into relevant biological functions. Conclusions: This study presents a novel framework for understanding lncRNA-TF-mediated gene regulation in PVTT. It identifies potential therapeutic targets and prognostic biomarkers that could facilitate the development of targeted therapies for PVTT, offering new opportunities to improve clinical outcomes.