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

IF 3.3 3区 医学 Q2 ONCOLOGY
Journal of Cancer Pub Date : 2025-02-11 eCollection Date: 2025-01-01 DOI:10.7150/jca.107270
Ji Young Kim, So Hee Dho, Lark Kyun Kim
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引用次数: 0

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.

门静脉肿瘤血栓形成中lncrna驱动网络的表征:对肝细胞癌进展的影响。
背景:门静脉肿瘤血栓形成(PVTT)是晚期肝细胞癌(HCC)常见且严重的并发症,常导致预后不良。尽管PVTT具有重要的临床意义,但驱动其形成的分子机制尚不清楚。长链非编码rna (lncRNAs)已成为PVTT进展的潜在贡献者,促使本研究探索lncRNAs作为PVTT的潜在生物标志物。方法:我们分析了来自基因表达综合数据库的公开数据集,以确定正常与HCC、正常与PVTT、HCC与PVTT三种比较中差异表达的lncrna和mrna。研究人员对转录谱进行了表征,并使用在线数据库筛选了与HCC和pvtt特异性lncrna相互作用的蛋白质,发现所有相互作用的蛋白质都是转录因子(tf)。我们通过将TF靶基因与来自每个比较的差异表达基因(DEGs)相交,构建了lncrna -TF靶基因调控网络。进行蛋白-蛋白相互作用(PPI)网络分析以确定关键簇和枢纽基因,突出显示了AR和ESR1等tf。通过基因本体分析,了解调控网络的生物学功能。结果:该研究确定了正常、HCC和PVTT样本中不同的转录谱。构建了涉及lncrna、tf和靶基因的关键调控网络,并确定了包括AR和ESR1在内的重要枢纽基因为潜在的治疗靶点。PPI网络分析揭示了与PVTT进展相关的重要聚类,而基因本体分析提供了相关生物学功能的见解。结论:本研究为理解lncrna - tf介导的PVTT基因调控提供了一个新的框架。它确定了潜在的治疗靶点和预后生物标志物,可以促进PVTT靶向治疗的发展,为改善临床结果提供新的机会。
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来源期刊
Journal of Cancer
Journal of Cancer ONCOLOGY-
CiteScore
8.10
自引率
2.60%
发文量
333
审稿时长
12 weeks
期刊介绍: Journal of Cancer is an open access, peer-reviewed journal with broad scope covering all areas of cancer research, especially novel concepts, new methods, new regimens, new therapeutic agents, and alternative approaches for early detection and intervention of cancer. The Journal is supported by an international editorial board consisting of a distinguished team of cancer researchers. Journal of Cancer aims at rapid publication of high quality results in cancer research while maintaining rigorous peer-review process.
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