Significance of tumour cell HLA-G5/-G6 isoform expression in discrimination for adenocarcinoma from squamous cell carcinoma in lung cancer patients

J Cell Mol Med. 2015 Apr;19(4):778-85. doi: 10.1111/jcmm.12400. Epub 2015 Feb 16.

Abstract

Human leucocyte antigen (HLA)-G has seven isoforms, of which HLA-G1-G4 are membrane-bound and HLA-G5-G7 are soluble. Previous studies reinforced HLA-G expression was strongly related to poor prognosis in different types of cancers. Among these studies, the monoclonal antibody (mAb) 4H84 was used which detects all HLA-G isoform heavy chain; unfortunately, leaves the specific types of isoforms expressed in lesions undistinguished and its clinical significance needs to be clarified. To explore clinical significance of lesion soluble HLA-G (sHLA-G) in non-small-cell lung cancer (NSCLC), mAb 5A6G7 recognizing HLA-G5/-G6 molecules was used. Tumour cell sHLA-G expression in 131 primary NSCLC lesions (66 squamous cell carcinoma, 55 adenocarcinoma and 10 adenosquamous carcinoma) were analysed with immunohistochemistry. Data showed that sHLA-G expression was observed in 34.0% (45/131) of the NSCLC lesions, which was unrelated to patient age, sex, lymph nodal status, tumour-node-metastasis stage and patient survival. However, tumour cell sHLA-G expression in lesions was predominately observed in adenocarcinoma lesions (73.0%, 40/55) which was significantly higher than that in squamous cell carcinoma (6.0%, 4/66) and adenosquamous carcinoma lesions (10.0%, 1/10, P < 0.001). The area under the receiver operating characteristic curve for lesion sHLA-G was 0.833 (95% CI: 0.754-0.912, P < 0.001) for adenocarcinoma versus squamous cell carcinoma. Our findings for the first time showed that tumour cell sHLA-G was predominately expressed in lung adenocarcinoma, which could be a useful biomarker to discriminate adenocarcinoma from squamous cell carcinoma in NSCLC patients.

Keywords: HLA-G; ROC; non-small-cell lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / diagnosis
  • Adenocarcinoma / metabolism*
  • Biomarkers, Tumor / biosynthesis
  • Blotting, Western
  • Carcinoma, Adenosquamous / diagnosis
  • Carcinoma, Adenosquamous / metabolism
  • Carcinoma, Squamous Cell / diagnosis
  • Carcinoma, Squamous Cell / metabolism*
  • Diagnosis, Differential
  • Female
  • Flow Cytometry
  • HLA-G Antigens / biosynthesis*
  • Humans
  • Immunohistochemistry / methods
  • Kaplan-Meier Estimate
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / metabolism*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • Protein Isoforms / biosynthesis
  • ROC Curve

Substances

  • Biomarkers, Tumor
  • HLA-G Antigens
  • Protein Isoforms