Organ Transplantation Center, The Affiliated Hospital of Qingdao University, 266003 Qingdao, Shandong, China.
The Institute of Transplantation Science, Qingdao University, 266003 Qingdao, Shandong, China.
Front Biosci (Landmark Ed). 2024 Aug 30;29(9):315. doi: 10.31083/j.fbl2909315.
Liver cancer is a highly lethal malignancy with frequent recurrence, widespread metastasis, and low survival rates. The aim of this study was to explore the role of Endoglin (ENG) in liver cancer progression, as well as its impacts on angiogenesis, immune cell infiltration, and the therapeutic efficacy of sorafenib.
A comprehensive evaluation was conducted using online databases Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA), 76 pairs of clinical specimens of tumor and adjacent non-tumor liver tissue, and tissue samples from 32 hepatocellular carcinoma (HCC) patients treated with sorafenib. ENG expression levels were evaluated using quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR), Western blot, and immunohistochemical analysis. Cox regression analysis, Spearman rank correlation analysis, and survival analysis were used to assess the results. Functional experiments included Transwell migration assays and tube formation assays with Human Umbilical Vein Endothelial Cells (HUVECs).
Tumor cells exhibited retro-differentiation into endothelial-like cells, with a significant increase in ENG expression in these tumor-derived endothelial cells (TDECs). High expression of ENG was associated with more aggressive cancer characteristics and worse patient prognosis. Pathway enrichment and functional analyses identified ENG as a key regulator of immune responses and angiogenesis in liver cancer. Further studies confirmed that ENG increases the expression of Collagen type Iα1 (COL1A1), thereby promoting angiogenesis in liver cancer. Additionally, HCC patients with elevated ENG levels responded well to sorafenib treatment.
This study found that ENG is an important biomarker of prognosis in liver cancer. Moreover, ENG is associated with endothelial cell differentiation in liver cancer and plays a crucial role in formation of the tumor vasculature. The assessment of ENG expression could be a promising strategy to identify liver cancer patients who might benefit from targeted immunotherapies.
肝癌是一种高度致命的恶性肿瘤，具有频繁复发、广泛转移和低生存率的特点。本研究旨在探讨内皮糖蛋白（ENG）在肝癌进展中的作用，及其对血管生成、免疫细胞浸润和索拉非尼治疗疗效的影响。
利用在线数据库基因表达综合数据库（GEO）和癌症基因组图谱（TCGA）、76 对肝癌组织及其相邻非肿瘤肝组织的临床标本、32 例接受索拉非尼治疗的肝细胞癌（HCC）患者的组织标本进行了综合评估。采用定量逆转录聚合酶链反应（qRT-PCR）、Western blot 和免疫组织化学分析评估 ENG 表达水平。采用 Cox 回归分析、Spearman 秩相关分析和生存分析进行评估。功能实验包括 Transwell 迁移实验和人脐静脉内皮细胞（HUVEC）的管形成实验。
肿瘤细胞表现出向内皮样细胞的逆行分化，这些肿瘤衍生的内皮细胞（TDECs）中 ENG 的表达显著增加。高表达 ENG 与更具侵袭性的癌症特征和更差的患者预后相关。通路富集和功能分析将 ENG 鉴定为肝癌中免疫反应和血管生成的关键调节因子。进一步的研究证实，ENG 增加了胶原 Iα1（COL1A1）的表达，从而促进了肝癌的血管生成。此外，ENG 水平升高的 HCC 患者对索拉非尼治疗反应良好。
本研究发现 ENG 是肝癌预后的重要生物标志物。此外，ENG 与肝癌中的内皮细胞分化有关，并在肿瘤血管形成中发挥关键作用。评估 ENG 表达可能是一种很有前途的策略，可以识别可能受益于靶向免疫治疗的肝癌患者。
