Elevated Preoperative Serum CEA Level Is Associated with Poor Prognosis in Patients with Hepatocellular Carcinoma Through the Epithelial-Mesenchymal Transition

Anticancer Res. 2017 Mar;37(3):1169-1175. doi: 10.21873/anticanres.11430.

Abstract

Background: Serum carcinoembryonic antigen (CEA) is used as an indicator of tumor progression in a variety of carcinomas. A subset of patients with hepatocellular carcinoma (HCC) exhibit increased serum CEA level, but the significance of this is unclear. In this study, we investigated the prognosis of patients with HCC with increased serum CEA, and explored the correlations with expression of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and epithelial-mesenchymal transition (EMT) and tumor angiogenesis.

Materials and methods: One hundred and twenty-three patients with HCC who underwent radical resection were divided into two groups according to a cut-off value of 5.0 ng/ml for serum CEA: high (n=24) and normal (n=99) groups. We compared the clinicopathological factors with serum CEA levels and its correlations with CEACAM1 expression, EMT-related factors and microvessel density (MVD) of tumor tissues by immunohistochemistry.

Results: In the high CEA group, the disease-free survival (DFS) rate was significantly worse than in the normal CEA group. Multivariate analysis revealed that a high CEA level was an independent factor predictive of recurrence. Furthermore, increased serum CEA levels were positively correlated with CEACAM1 expression. Moreover, CEACAM1 expression was positively correlated with expression of EMT-related factors and MVD of tumor tissues.

Conclusion: Increased serum CEA level reflected CEACAM1 expression and was an independent factor predictive of recurrence in HCC through EMT and tumor angiogenesis.

Keywords: CEA; CEACAM; epithelial mesenchymal transition; hepatocellular carcinoma.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD / metabolism
  • Antigens, CD34 / metabolism
  • Cadherins / metabolism
  • Carcinoembryonic Antigen / blood*
  • Carcinoma, Hepatocellular / blood*
  • Carcinoma, Hepatocellular / surgery
  • Cell Adhesion Molecules / metabolism
  • Disease-Free Survival
  • Epithelial-Mesenchymal Transition*
  • Female
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Liver Neoplasms / blood*
  • Liver Neoplasms / surgery
  • Male
  • Microcirculation
  • Middle Aged
  • Neovascularization, Pathologic*
  • Predictive Value of Tests
  • Preoperative Period
  • Prognosis
  • Recurrence
  • Vimentin / metabolism

Substances

  • Antigens, CD
  • Antigens, CD34
  • CD66 antigens
  • CDH1 protein, human
  • Cadherins
  • Carcinoembryonic Antigen
  • Cell Adhesion Molecules
  • Vimentin