Combined analysis of HLA class I, HLA-E and HLA-G predicts prognosis in colon cancer patients

Br J Cancer. 2014 Jan 21;110(2):459-68. doi: 10.1038/bjc.2013.696. Epub 2013 Nov 5.

Abstract

Background: Evasion of immune surveillance and suppression of the immune system are important hallmarks of tumour development in colon cancer. The goal of this study was to establish a tumour profile based on biomarkers that reflect a tumour's immune susceptibility status and to determine their relation to patient outcome.

Methods: The study population consisted of 285 stage I-IV colon cancer patients of which a tissue micro array (TMA) was available. Sections were immunohistochemically stained for the presence of Foxp3+ cells and tumour expression of HLA Class I (HLA-A, -B, -C) and non-classical HLA-E and HLA-G. All markers were combined for further analyses, resulting in three tumour immune phenotypes: strong immune system tumour recognition, intermediate immune system tumour recognition and poor immune system tumour recognition.

Results: Loss of HLA class I expression was significantly related to a better OS (P-value 0.005) and DFS (P-value 0.008). Patients with tumours who showed neither HLA class I nor HLA-E or -G expression (phenotype a) had a significant better OS and DFS (P-value <0.001 and 0.001, respectively) compared with phenotype b (OS HR: 4.7, 95% CI: 1.2-19.0, P=0.001) or c (OS HR: 8.2, 95% CI: 2.0-34.2, P=0.0001). Further, the tumour immune phenotype was an independent predictor for OS and DFS (P-value 0.009 and 0.013, respectively).

Conclusion: Tumours showing absence of HLA class I, HLA-E and HLA-G expressions were related to a better OS and DFS. By combining the expression status of several immune-related biomarkers, three tumour immune phenotypes were created that related to patient outcome. These immune phenotypes represented significant, independent, clinical prognostic profiles in colon cancer.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / immunology
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / immunology*
  • Colonic Neoplasms / pathology
  • Female
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / immunology
  • Genes, MHC Class I / immunology*
  • HLA-G Antigens / genetics
  • HLA-G Antigens / immunology*
  • Histocompatibility Antigens Class I / genetics*
  • Histocompatibility Antigens Class I / immunology*
  • Humans
  • Male
  • Middle Aged
  • Prognosis

Substances

  • Biomarkers, Tumor
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • HLA-E antigen
  • HLA-G Antigens
  • Histocompatibility Antigens Class I