ENG is a Biomarker of Prognosis and Angiogenesis in Liver Cancer, and Promotes the Differentiation of Tumor Cells into Vascular ECs

Shangheng Shi; Cunle Zhu; Yue Hu; Peng Jiang; Jinxin Zhao; Qingguo Xu

doi:10.31083/j.fbl2909315

Frontiers in Bioscience-Landmark (Aug 2024)

ENG is a Biomarker of Prognosis and Angiogenesis in Liver Cancer, and Promotes the Differentiation of Tumor Cells into Vascular ECs

Shangheng Shi,
Cunle Zhu,
Yue Hu,
Peng Jiang,
Jinxin Zhao,
Qingguo Xu

Affiliations

Shangheng Shi: Organ Transplantation Center, The Affiliated Hospital of Qingdao University, 266003 Qingdao, Shandong, China
Cunle Zhu: Organ Transplantation Center, The Affiliated Hospital of Qingdao University, 266003 Qingdao, Shandong, China
Yue Hu: Hepatobiliary and Pancreatic Surgery Department, Affiliated First Hospital of Ningbo University, 315000 Ningbo, Zhejiang, China
Peng Jiang: Organ Transplantation Center, The Affiliated Hospital of Qingdao University, 266003 Qingdao, Shandong, China
Jinxin Zhao: Organ Transplantation Center, The Affiliated Hospital of Qingdao University, 266003 Qingdao, Shandong, China
Qingguo Xu: Organ Transplantation Center, The Affiliated Hospital of Qingdao University, 266003 Qingdao, Shandong, China

DOI: https://doi.org/10.31083/j.fbl2909315
Journal volume & issue: Vol. 29, no. 9
p. 315

Abstract

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Background: 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. Methods: 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). Results: 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. Conclusions: 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.

Published in Frontiers in Bioscience-Landmark

ISSN: 2768-6701 (Print); 2768-6698 (Online)
Publisher: IMR Press
Country of publisher: Singapore
LCC subjects: Science: Chemistry: Organic chemistry: Biochemistry; Science: Biology (General)
Website: https://www.imrpress.com/journal/FBL

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