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.

Keywords: HLA-G; cervical cancer; gynecological cancer; human papillomavirus infection; meta-analysis; polymorphism; sHLA-G.