title: The association of renin-angiotensin system genes with the progression of hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Angiogenesis is reported to play a pivotal role in the occurrence, development and metastasis of HCC. The renin-angiotensin system (RAS) is involved in the regulation of angiogenesis. Here, based on the analysis of HCC datasets from Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA), we found that there was a negative correlation between the mRNA levels of angiotensin converting enzyme 2 (ACE2) and CD34. To explore the association of RAS with the progression from fibrosis to cirrhosis to HCC, liver specimens and serum samples were collected from patients with hepatic fibrosis, cirrhosis and HCC. Relative hepatic mRNA levels of CD34 and ACE2 were determined by real-time PCR, and the serum concentrations of Angiotensin II (Ang II), Ang (1-7) and vascular endothelial growth factor (VEGF) were detected by ELISA. We found that ACE2 mRNA was gradually decreased, while CD34 mRNA was progressively increased with the increasing grade of disease severity. Concentrations of Ang II, Ang (1-7) and VEGF were higher in the sera of patients than in that of healthy volunteers. These proteins' concentrations were also progressively increased with the increasing grade of disease severity. Moreover, a positive correlation was found between VEGF and Ang II or Ang (1-7), while negative correlation was observed between mRNA levels of CD34 and ACE2. More importantly, patients with higher level of ACE2 expression had longer survival time than those with lower level of ACE2 expression. Taken together, our data suggests that the low expression of ACE2 may be a useful indicator of poor prognosis in HCC. The RAS may have a role in the progression of HCC.
authors.affiliation: Department of Hepatobiliary Surgery, The People's Hospital of Lishui, The Sixth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, PR China.
authors.forename: Guanxiong
authors.initials: G
authors.lastname: Ye
authors.affiliation: Department of Hepatobiliary Surgery, The People's Hospital of Lishui, The Sixth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, PR China. Electronic address: bingmayong811@163.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Department of Hepatobiliary Surgery, The People's Hospital of Lishui, The Sixth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, PR China.
authors.forename: Xianghong
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Hepatobiliary Surgery, The People's Hospital of Lishui, The Sixth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, PR China.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Hepatobiliary Surgery, The People's Hospital of Lishui, The Sixth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, PR China.
authors.forename: Shengqian
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Hepatobiliary Surgery, The People's Hospital of Lishui, The Sixth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, PR China.
authors.forename: Chengjun
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Hepatobiliary Surgery, The People's Hospital of Lishui, The Sixth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, PR China.
authors.forename: Xinmei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Hepatobiliary Surgery, The People's Hospital of Lishui, The Sixth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, PR China.
authors.forename: Shi
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Hepatobiliary Surgery, The People's Hospital of Lishui, The Sixth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, PR China.
authors.forename: Debiao
authors.initials: D
authors.lastname: Pan
mesh_terms: D000803:Angiotensin I / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D000085962:Angiotensin-Converting Enzyme 2; D018952:Antigens, CD34 / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016022:Case-Control Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000235:genetics / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D010446:Peptide Fragments / Q000097:blood; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011379:Prognosis; D012016:Reference Values; D012084:Renin-Angiotensin System / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D018952:Antigens, CD34; D014408:Biomarkers, Tumor; D010446:Peptide Fragments; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000804:Angiotensin II; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2; C118790:angiotensin I (1-7)
keywords: ACE2; Angiogenesis; Cirrhosis; Fibrosis; Hepatocellular carcinoma; VEGF