PDF(Pubmed)
Abstract：
Introduction: Hepatocellular carcinoma (HCC) is responsible for approximately 90% of liver malignancies and is the third most common cause of cancer-related mortality worldwide. However, the role of anoikis, a programmed cell death mechanism crucial for maintaining tissue equilibrium, is not yet fully understood in the context of HCC. Methods: Our study aimed to investigate the expression of 10 anoikis-related genes (ARGs) in HCC, including BIRC5, SFN, UBE2C, SPP1, E2F1, etc., and their significance in the disease. Results: Through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, we discovered that these ARGs are involved in important processes such as tissue homeostasis, ion transport, cell cycle regulation, and viral infection pathways. Furthermore, we found a significant correlation between the prognostic value of five ARGs and immune cell infiltrates. Analysis of clinical datasets revealed a strong association between BIRC5 expression and HCC pathological progression, including pathological stage, T stage, overall survival (OS), and race. By constructing a competing endogenous RNA (ceRNA) network and using molecular docking, we identified ten bioactive compounds from traditional Chinese medicine (TCM) that could potentially modulate BIRC5. Subsequent in vitro experiments confirmed the influence of platycodin D, one of the identified compounds, on key elements within the ceRNA network. Discussion: In conclusion, our study presents a novel framework for an anoikis-centered prognostic model and an immune-involved ceRNA network in HCC, revealing potential regulatory targets. These insights contribute to our understanding of HCC pathology and may lead to improved therapeutic interventions.
摘要：
简介：肝细胞癌（HCC）约占肝脏恶性肿瘤的90％，是全球癌症相关死亡率的第三大常见原因。然而,Anoikis的作用,对维持组织平衡至关重要的程序性细胞死亡机制，在HCC的背景下还没有完全理解。方法：我们的研究旨在探讨10个失巢凋亡相关基因（ARGs）在肝癌中的表达，包括BIRC5，SFN，UBE2C,SPP1、E2F1等.,以及它们在疾病中的意义。结果：通过基因本体论（GO）和京都基因和基因组百科全书（KEGG）途径分析，我们发现这些ARGs参与了重要的过程，如组织稳态，离子传输，细胞周期调节，和病毒感染途径。此外，我们发现5种ARGs的预后价值与免疫细胞浸润之间存在显著相关性.临床数据集的分析揭示了BIRC5表达与HCC病理进展之间的强关联，包括病理阶段，T级,总生存期（OS），和种族。通过构建竞争性内源RNA(ceRNA)网络,利用分子对接,我们从中药（TCM）中鉴定出10种可能潜在地调节BIRC5的生物活性化合物。随后的体外实验证实了桔梗皂苷D的影响，确定的化合物之一，在ceRNA网络中的关键元素上。讨论：总之，我们的研究提出了一个新的框架，一个以anoikis为中心的预后模型和一个免疫参与的ceRNA网络在HCC，揭示潜在的监管目标。这些见解有助于我们对HCC病理学的理解，并可能导致改进的治疗干预措施。
