Clinical significance and molecular mechanism of angiotensin-converting enzyme 2 in hepatocellular carcinoma tissues

Bioengineered. 2021 Dec;12(1):4054-4069. doi: 10.1080/21655979.2021.1952791.

Abstract

During the pandemic of the coronavirus disease 2019, there exist quite a few studies on angiotensin-converting enzyme 2 (ACE2) and SARS-CoV-2 infection, while little is known about ACE2 in hepatocellular carcinoma (HCC). The detailed mechanism among ACE2 and HCC still remains unclear, which needs to be further investigated. In the current study with a total of 6,926 samples, ACE2 expression was downregulated in HCC compared with non-HCC samples (standardized mean difference = -0.41). With the area under the curve of summary receiver operating characteristic = 0.82, ACE2 expression showed a better ability to differentiate HCC from non-HCC. The mRNA expression of ACE2 was related to the age, alpha-fetoprotein levels and cirrhosis of HCC patients, and it was identified as a protected factor for HCC patients via Kaplan-Meier survival, Cox regression analyses. The potential molecular mechanism of ACE2 may be relevant to catabolic and cell division. In all, decreasing ACE2 expression can be seen in HCC, and its protective role for HCC patients and underlying mechanisms were explored in the study.

Keywords: ACE2; COVID-19; hepatocellular carcinoma.

MeSH terms

  • Age Factors
  • Aged
  • Angiotensin-Converting Enzyme 2 / genetics*
  • Angiotensin-Converting Enzyme 2 / metabolism
  • Area Under Curve
  • COVID-19 / virology
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology
  • Databases, Genetic
  • Datasets as Topic
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Cirrhosis / diagnosis
  • Liver Cirrhosis / genetics*
  • Liver Cirrhosis / mortality
  • Liver Cirrhosis / pathology
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Proteins / classification
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Protective Factors
  • Protein Interaction Mapping
  • ROC Curve
  • Receptors, Virus / genetics*
  • Receptors, Virus / metabolism
  • SARS-CoV-2 / pathogenicity
  • Survival Analysis
  • alpha-Fetoproteins / genetics*
  • alpha-Fetoproteins / metabolism

Substances

  • AFP protein, human
  • Neoplasm Proteins
  • Receptors, Virus
  • alpha-Fetoproteins
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2

Grants and funding

National Natural Science Foundation of China (NSFC 81860717), Natural Science Foundation of Guangxi, China (2019GXNSFAA245074, 2018GXNSFAA294025), Guangxi Medical High-level Key Talents Training ‘139’ Program (2020), Guangxi Zhuang Autonomous Region Health Committee Self-Financed Scientific Research Project (Z20190529, Z20190523, Z20210442), Guangxi Educational Science Planning Key Project (2021B167), Guangxi Higher Education Undergraduate Teaching Reform Project (2020JGA146), Guangxi Medical University Education and Teaching Reform Project (2019XJGZ04), Guangxi Medical University Training Program for Distinguished Young Scholars (2017), Medical Excellence Award Funded by the Creative Research Development Grant from the First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University Student Innovation and Entrepreneurship Training Program Project (202010598011).