PSG9 promotes angiogenesis by stimulating VEGFA production and is associated with poor prognosis in hepatocellular carcinoma

Sci China Life Sci. 2017 May;60(5):528-535. doi: 10.1007/s11427-016-0226-7. Epub 2017 Jan 4.

Abstract

Hepatocellular carcinoma (HCC) is a common malignant solid tumor characterized by rich vascularization. Pregnancy-specific glycoprotein 9 (PSG9) is a member of the carcinoembryonic antigen (CEA)/PSG family and is produced at high levels during pregnancy. We previously identified PSG9 as an HCC-related protein. However, the expression of PSG9 and its regulation during HCC carcinogenesis remain poorly explored. In the present study, we first found that the levels of PSG9 protein were significantly increased in the plasma of HCC patients. PSG9 overexpression also increased the proliferation ability of an HCC cell line. High expression of PSG9 was associated with angiogenesis by accelerating VEGFA expression. In addition, Cox's proportional hazards model analysis revealed that the plasma level of PSG9 was an independent prognostic factor for overall survival. We propose that PSG9 is a novel indicator of prognosis in patients with HCC and could serve as a novel therapeutic target for HCC. Furthermore, our results indicate that PSG9 protein may facilitate the development of HCC by fostering angiogenesis via promoting VEGFA production in cancer cells.

Keywords: PSG9; VEGFA; angiogenesis; hepatocellular carcinoma (HCC).

MeSH terms

  • Carcinoma, Hepatocellular / blood supply
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Liver Neoplasms / blood supply
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Male
  • Middle Aged
  • Neovascularization, Pathologic / blood
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism*
  • Pregnancy-Specific beta 1-Glycoproteins / classification
  • Pregnancy-Specific beta 1-Glycoproteins / genetics
  • Pregnancy-Specific beta 1-Glycoproteins / metabolism*
  • Prognosis
  • RNA Interference
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Pregnancy-Specific beta 1-Glycoproteins
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A