The relationship of 3′UTR HLA‐G14‐bp insertion/deletion and +3142 C/G polymorphisms and soluble HLA‐G expression with gynecological cancers: An updated meta‐analysis

Abstract

Objectives Human leukocyte antigen‐G (HLA‐G) is implicated in several cancers and is considered to be an immune checkpoint regulator. We determined the association between polymorphisms in the 3′ untranslated region of HLA‐G and soluble HLA‐G (sHLA‐G) expression with gynecological cancers (GCs). Methods A meta‐analysis was conducted to examine the association between HLA‐G14‐bp insertion ( I )/ deletion ( D ) and +3142C/G polymorphism in GC and to evaluate sHLA‐G expression Results We revealed a significant association between the +3142C/G polymorphism and invasive cervical cancer (ICC) based on the allelic model G versus C (odds ratio [OR] = 0.738, 95% confidence interval [CI] = 0.563–0.966, p = 0.027), dominant GG+GC versus CC (OR = 0.584, 95% CI = 0.395–0.862, p = 0.007), and codominant GG versus CC (OR = 0.527, 95% CI = 0.312–0.891, p = 0.017) models, suggesting that the G allele and GG genotype are protective against ICC. In gynecological precancerous patients with human papillomavirus (HPV) infection, we found that the 14‐bp I/D under the codominant DD versus DI model (OR = 0.492, 95% CI = 0.241–1.004, p = 0.051) was of borderline significance. Soluble HLA‐G levels were significantly higher in patients compared with healthy controls (standardized mean differences [SMD] = 1.434, 95% CI = 0.442–2.526, p = 0.005). Stratification by cancer type revealed that the sHLA‐G levels were significantly increased in cervical cancer (SMD = 4.889, 95% CI = 0.468–9.310, p = 0.030) and in subjects of Asian ethnicity (SMD = 4.889, 95% CI = 0.467–9.309, p = 0.030). Conclusions HLA‐G14‐bp I/D and +3142 C/G polymorphisms are associated with GC and HPV‐associated cervical cancer. In addition, we found significantly increased sHLA‐G levels in cancer patients. These results provide a basis for further studies in diagnostics and immunotherapy of GC.

HLA-G High-expressor 3’UTR Markers Are Linked to Gastric Cancer Development and Survival

“…Other works and meta-analysis described an association of HLA-G 3'UTR haplotypes to the development and severity of different malignancies, such as breast and colorectal cancer, were 14bp Del/Del and + 3142 C/C, both forming UTR-1 and UTR6 haplotypes, showed association to risk of developing both cancers (20,21). Moreover, other authors showed an association of HLA-G levels of expression and the 14bp polymorphism in gynecologic cancers (22), and, in the same vein of thinking, loss of miR-152 increases HLA-G expression in vitro (23), mimicking the effect of + 3142 polymorphisms, as miR-152 is not able to bind + 3142 C/C. All these ndings not only support the results of our work, but also provide a functional explanation for them, as it seems clear that there is a link between variants in the 3'UTR of HLA-G and the expression levels of this protein and, consequently, with the risk of developing tumors of epithelial origin.…”

HLA-G 3’UTR polymorphism diplotypes and soluble HLA-G plasma levels impact cervical cancer susceptibility and prognosis

“…In addition, several studies have debated the regulation of sHLA-G levels by HLA-G 3’UTR polymorphisms. These disputes may vary among different populations with different genetic backgrounds ( 17 , 28 , 29 ).…”

Human leukocyte antigen‐G in gynaecological tumours

“…A recently published meta‐analysis confirmed that HLA‐G+3142 C/G is significantly associated with reduced susceptibility to cervical cancer. Similarly, HLA‐G14‐bp I/D was found to be significantly associated with HPV‐induced cervical prelesions (Tizaoui et al., 2022).…”

“…A recently published meta-analysis confirmed that HLA-G+3142 C/G is significantly associated with reduced susceptibility to cervical cancer. Similarly, HLA-G14-bp I/D was found to be significantly associated with HPV-induced cervical prelesions(Tizaoui et al, 2022).Third, the upregulation of HLA-G expression favours the persistence of HPV in a microenvironment of a submissive host response Xu et al (2018). showed that significantly increased prevalence of HLA-G* 3′ UTR 14-bp ins among 495 Chinese Han women infected with HPV18 (38.5% vs. 29.2%, p < .05; OR, 1.52) was associated with the progression of HPV18-related cervical lesions.…”