title: Human Leukocyte Antigen G Polymorphism and Expression Are Associated with an Increased Risk of Non-Small-Cell Lung Cancer and Advanced Disease Stage.
abstract: Human leukocyte antigen (HLA)-G acts as negative regulator of the immune responses and its expression may enable tumor cells to escape immunosurveillance. The purpose of this study was to investigate the influence of HLA-G allelic variants and serum soluble HLA-G (sHLA-G) levels on risk of non-small-cell lung cancer (NSCLC). We analyzed 191 Caucasian adults with NSCLC and 191 healthy subjects recruited between January 2009 and March 2014 in Ariana (Tunisia). Serum sHLA-G levels were measured by immunoassay and HLA-G alleles were determined using a direct DNA sequencing procedures. The heterozygous genotypes of HLA-G 010101 and -G 010401 were associated with increased risks of both NSCLC and advanced disease stages. In contrast, the heterozygous genotypes of HLA-G 0105N and -G 0106 were associated with decreased risks of NSCC and clinical disease stage IV, respectively. Serum sHLA-G levels were significantly higher in patients with NSCLC and particularly in those with advanced disease stages compared to healthy subjects. The area under the receiver-operating characteristic (ROC) curves was 0.82 for controls vs patients. Given 100% specificity, the highest sensitivity achieved to detect NSCLC was 52.8% at a cutoff value of 24.9 U/ml. Patients with the sHLA-G above median level (≥ 50 U/ml) had a significantly shorter survival time. This study demonstrates that HLA-G allelic variants are independent risk factors for NSCLC. Serum sHLA-G levels in NSCLC patients could be useful biomarkers for the diagnostic and prognosis of NSCLC.
authors: Tunis El Manar University, Medicine Faculty of Tunis, Department of Immunology and Histology, Tunis, Tunisia.
authors: Amira
authors: A
authors: Ben Amor
authors: Laboratoire d'immunogénétique, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Canada.
authors: Karine
authors: K
authors: Beauchemin
authors: Laboratoire d'immunogénétique, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Canada.
authors: Marie-Claude
authors: MC
authors: Faucher
authors: Tunis El Manar University, Medicine Faculty of Tunis, Department of Immunology and Histology, Tunis, Tunisia.|Abderrahmen Mami Hospital, Unit Research UR/12SP15 (Homeostasis and cell immune dysfunction), Ariana, Tunisia.
authors: Agnes
authors: A
authors: Hamzaoui
authors: Tunis El Manar University, Medicine Faculty of Tunis, Department of Immunology and Histology, Tunis, Tunisia.|Abderrahmen Mami Hospital, Unit Research UR/12SP15 (Homeostasis and cell immune dysfunction), Ariana, Tunisia.
authors: Kamel
authors: K
authors: Hamzaoui
authors: Laboratoire d'immunogénétique, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Canada.|Département de Microbiologie et Immunologie de l'Université de Montréal, Montreal, Canada.
authors: Michel
authors: M
authors: Roger
mesh_terms: D015415:Biomarkers / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D059951:HLA-G Antigens / Q000097:blood* / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D012372:ROC Curve
chemical_list: D015415:Biomarkers; D059951:HLA-G Antigens