ABSTRACT
Aim: Human Leukocyte Antigen-G (HLA-G) is a non-classical class I molecule that is involved in maternal-fetal immunotolerance. In cancer, this molecule contributes to the tumor escape. The aim of this study was to evaluate the 14 bp In/Del and +3142 C > G polymorphisms of the HLA-G 3' UTR and its relation with plasma and tissue HLA-G expression in patients with grade IV (high-grade) and grade I/II (low-grade) gliomas and controls.Patients and methods: Peripheral blood and tumor biopsies were collected from 85 patients with gliomas and blood samples from 94 controls. Polymorphisms were analyzed from blood DNA. Soluble HLA-G (sHLA-G) was measured by ELISA in plasma of the subjects and the tissue expression by immunohistochemistry on patient's tissue.Results: Higher levels of sHLA-G were observed in grade IV gliomas patients than in controls (p < 0.0001). In grade IV patients, the heterozygous 14pb In/Del, +3142 C/G genotypes and Del/C*In/G haplotype were associated with higher sHLA-G levels (p < 0.0001) when compared with controls. GBM patients were stratified into high and low sHLA-G expression and an association was found between +3142 C allele and high sHLA-G plasmatic levels (p = 0.0095). Tissue HLA-G immunolabel was higher in high-grade than low-grade gliomas (p = 0.0033).Conclusion: This was the first study evaluating HLA-G 3' UTR polymorphisms and expression in patients with gliomas. The 14 bp In/Del and +3142 C/G genotypes and haplotypes showed high influence over sHLA-G expression, suggesting a heterozygous advantage in the tumor context and may contribute to a worse prognosis in glioma patients.
Subject(s)
Brain Neoplasms/genetics , Brain Neoplasms/metabolism , Glioma/genetics , Glioma/metabolism , HLA-G Antigens/blood , 3' Untranslated Regions , Adult , Brain Mapping , Child , Female , Genotype , Humans , Male , Middle AgedABSTRACT
Besides HPV infection, the progression to cervical cancer also depends on the host immune response. HLA-G molecules are involved in the inhibition of cell-mediated immune responses and may permit the development of an infection in the female cervical tract. The aim of this study was to explore the possible influence of the two HLA-G polymorphisms located on the 3'UTR on the susceptibility to cervical cancer and risk factors in Brazilian patients. Polymorphism analysis (14 bp In/Del and +3142C/G) was performed by PCR. A total of 105 cervical samples were tested, 50 without lesions and 55 with lesions; 22 with high grade (HSIL) and 33 with invasive cancer (ICC). The polymorphisms (∗)Del/Del was associated with a decreased risk of developing ICC in smokers and (∗)In and (∗)In/In were associated with an increased risk of HSIL and a higher risk of ICC in smokers. The genotype (∗)In/Del was associated with the increased risk of HSIL only among women with a family history of cancer. The haplotypes (∗)In/G and (∗)Del/G were associated with increased and decreased risk of HSIL and cervical cancer, respectively. In conclusion, the 3'UTR of HLA-G is associated with an increased risk of developing cervical cancer, especially in smokers.
