HLA-G 3′ untranslated region variants +3187G/G, +3196G/G and +3035T define diametrical clinical status and disease outcome in epithelial ovarian cancer

• Published in: Scientific reports 2019-04, Vol.9 (1), p.5407, Article 5407
• Main Authors: Schwich, Esther, Rebmann, Vera, Michita, Rafael Tomoya, Rohn, Hana, Voncken, Jan Willem, Horn, Peter A., Kimmig, Rainer, Kasimir-Bauer, Sabine, Buderath, Paul
• Format: Article
• Language: English
• Subjects: 13; 13/51; 3' Untranslated regions; 3' Untranslated Regions - genetics; 38; 38/23; 38/77; 45; 631/250/248; 631/250/580; 692/4028/67/1517/1709; Adult; Aged; Aged, 80 and over; Alleles; Carcinoma, Ovarian Epithelial - genetics; Carcinoma, Ovarian Epithelial - metabolism; Carcinoma, Ovarian Epithelial - pathology; Female; Gene Frequency; Genetic Predisposition to Disease - genetics; Genotype; Genotypes; Haplotypes; Histocompatibility antigen HLA; HLA-G Antigens - genetics; HLA-G Antigens - metabolism; Homozygosity; Humanities and Social Sciences; Humans; Kaplan-Meier Estimate; Metastases; Middle Aged; multidisciplinary; Neoplasm Staging; Ovarian cancer; Ovarian Neoplasms - genetics; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Polymorphism, Single Nucleotide; Science; Science (multidisciplinary); Single-nucleotide polymorphism; Tumor cells
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-41900-z

Expression of the non-classical human leukocyte antigen-G (HLA-G) promotes cancer progression in various malignancies including epithelial ovarian cancer (EOC). As single nucleotide polymorphisms (SNPs) in the HLA-G 3′ untranslated region (UTR) regulate HLA-G expression, we investigated HLA-G 3′UTR haplotypes arranged by SNPs in healthy controls (n = 75) and primary EOC patients (n = 79) and determined soluble HLA-G (sHLA-G) levels. Results were related to the clinical status and outcome. Although haplotype frequencies were similar in patients and controls, (i) sHLA-G levels were increased in EOC independent of the haplotype, (ii) homozygosity for UTR-1 or UTR-2 genotypes were significantly associated with metastases formation and presence of circulating tumor cells before therapy, whereas (iii) the UTR-5 and UTR-7 haplotypes were significantly associated with a beneficial clinical outcome regarding negative nodal status, early FIGO staging, and improved overall survival. Lastly, (iv) the ambivalent impact on clinical EOC aspects could be deduced to specific SNPs in the HLA-G 3′UTR: +3187G, +3196G and +3035T alleles. Our results give evidence that even if the genetic background of the HLA-G 3′UTR is identical between patients and controls, certain SNPs have the potential to contribute to diametrical clinical status/outcome in EOC.