title: Significance of tumour cell HLA-G5/-G6 isoform expression in discrimination for adenocarcinoma from squamous cell carcinoma in lung cancer patients.
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.
authors.affiliation: Medical Research Center, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Zhejiang, China.
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Yan
authors.forename: Di
authors.initials: D
authors.lastname: Liu
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Lu
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Li
authors.forename: Xia
authors.initials: X
authors.lastname: Zhang
authors.forename: Aifen
authors.initials: A
authors.lastname: Lin
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D015153:Blotting, Western; D018196:Carcinoma, Adenosquamous / Q000175:diagnosis / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000378:metabolism*; D003937:Diagnosis, Differential; D005260:Female; D005434:Flow Cytometry; D059951:HLA-G Antigens / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D020033:Protein Isoforms / Q000096:biosynthesis; D012372:ROC Curve
chemical_list: D014408:Biomarkers, Tumor; D059951:HLA-G Antigens; D020033:Protein Isoforms
keywords: HLA-G; ROC; non-small-cell lung cancer