Expression and prognosis role of indoleamine 2,3-dioxygenase in hepatocellular carcinoma

J Cancer Res Clin Oncol. 2008 Nov;134(11):1247-53. doi: 10.1007/s00432-008-0395-1. Epub 2008 Apr 26.

Abstract

Purpose: Immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO) plays an important role in immune tolerance. In some malignancies, the evidences were given to show that overexpression of IDO was related to poor prognosis of cancer patients.

Methods: In this study, we investigated IDO expression in hepatocellular carcinoma (HCC) cell lines and 138 primary HCC clinical surgical specimens, and correlation of IDO expression with clinical outcomes and prognosis of HCC patients.

Results: Reverse transcription-PCR analysis showed that in vitro IDO expression in HCC cell lines and non-cancerous liver cell line were dependent on IFN-gamma. Immunohistochemical detection revealed that IDO was overexpressed in 49 of 138 (35.5%) tumor resection samples, whereas 89 of 138 (64.5%) cases showed weak immunostaining. IDO overexpression was significantly correlated with high metastasis rates (P = 0.049). Kaplan-Meier survival curves showed that overexpression of IDO resulted in significantly poor prognosis (P = 0.017, log-rank test). Multivariate Cox's analysis showed that IDO expression was an independent prognostic factor for overall survival of HCC patients (P = 0.010).

Conclusion: Our data indicated that IDO may be a novel favorable prognostic indicator and candidate adjuvant therapeutic target for HCC.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Carcinoma, Hepatocellular / enzymology
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / therapy
  • Cell Line, Tumor
  • DNA Primers
  • Female
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / genetics*
  • Liver Neoplasms / enzymology
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Liver Neoplasms / therapy
  • Male
  • Middle Aged
  • Prognosis
  • RNA, Neoplasm / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Analysis
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • DNA Primers
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • RNA, Neoplasm