AUTHOR=Xu Fangfang , Tian Dandan , Shi Xiaoyang , Sun Kai , Chen Yuqing 

TITLE=Analysis of the Expression and Prognostic Potential of a Novel Metabolic Regulator ANGPTL8/Betatrophin in Human Cancers

JOURNAL=Pathology and Oncology Research

VOLUME=Volume 27 - 2021

YEAR=2021

URL=https://www.por-journal.com/journals/pathology-and-oncology-research/articles/10.3389/pore.2021.1609914

DOI=10.3389/pore.2021.1609914

ISSN=1532-2807

ABSTRACT=The angiopoietin-like protein (ANGPTL) family members, except for the novel atypical member ANGPTL8/betatrophin, have been reported to participate in angiogenesis, inflammation and cancer. ANGPTL8/betatrophin is a metabolic regulator that is involved in lipid metabolism and glucose homeostasis. However, little is known about the expression and prognostic value of ANGPTL8/betatrophin in human cancers. In this study, we first conducted detailed analyses of cancer versus normal samples. The mRNA and protein expression levels of ANGPTL8/betatrophin in different kinds of cancers were analyzed via the Human Protein Atlas (HPA), Gene Expression Profiling Interactive Analysis (GEPIA) and UALCAN-Clinical Proteomic Tumor Analysis Consortium (UALCAN-CPTAC) databases. The results revealed that the mRNA expression levels of ANGPTL8/betatrophin were significantly decreased in breast invasive carcinoma (BRCA) and cholangiocarcinoma (CHOL) samples compared with normal control samples. Moreover, ANGPTL8/betatrophin was highly expressed at the mRNA level in the HepG2 and MCF7 cancer cell lines. The protein expression level of ANGPTL8/betatrophin was significantly decreased in clear cell renal cell carcinoma (ccRCC) samples compared with normal control samples. Based on the expression profiles, the prognostic value was evaluated with the GEPIA database. The results of survival analyses demonstrated that high expression of ANGPTL8/betatrophin indicated better disease-free survival (DFS) than low expression in sarcoma (SARC), thymoma (THYM), and uterine carcinosarcoma (UCS), while high ANGPTL8/betatrophin expression was significantly related to poorer overall survival (OS) in kidney renal clear cell carcinoma (KIRC), pheochromocytoma and paraganglioma (PCPG) and poorer DFS in lung squamous cell carcinoma (LUSC). Moreover, ANGPTL8/betatrophin may potentially play a role in KIRC tumor staging and lung adenocarcinoma (LUAD) tumor grading. Analysis of gene regulation networks with the GeneMANIA, Metascape and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) databases suggested that ANGPTL8/betatrophin is mainly involved in angiogenesis; lipid homeostasis, especially triglyceride and cholesterol metabolism; glucose metabolism; the acute phase response; the inflammatory response; the PPAR signaling pathway; and several other signaling pathways. In conclusion, ANGPTL8/betatrophin expression was significantly different between cancer and normal tissues and could be a promising prognostic biomarker and therapeutic target, providing evidence to support further exploration of its mechanism in carcinogenesis and the development of defined human cancers.