Laboratory Microorganismes and Active Biomolecules, Sciences Faculty of Tunis, University of Tunis El Manar, Tunis, Tunisia.
Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia.
Immun Inflamm Dis. 2022 Jul;10(7):e645. doi: 10.1002/iid3.645.
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).
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).
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.
人类白细胞抗原-G（HLA-G）与多种癌症有关，被认为是免疫检查点调节剂。我们确定了 HLA-G 3'非翻译区的多态性与可溶性 HLA-G（sHLA-G）表达与妇科癌症（GC）之间的关联。
进行荟萃分析以检查 HLA-G14-bp 插入（I）/缺失（D）与+3142C/G 多态性与 GC 之间的关联，并评估 sHLA-G 表达结果。
基于等位基因模型 G 对 C（比值比[OR] = 0.738，95%置信区间[CI] = 0.563-0.966，p = 0.027）、显性 GG+GC 对 CC（OR = 0.584，95%CI = 0.395-0.862，p = 0.007）和共显性 GG 对 CC（OR = 0.527，95%CI = 0.312-0.891，p = 0.017）模型，我们发现+3142C/G 多态性与浸润性宫颈癌（ICC）显著相关，提示 G 等位基因和 GG 基因型可预防 ICC。在 HPV 感染的妇科癌前患者中，我们发现 14-bp I/D 在共显性 DD 对 DI 模型下（OR = 0.492，95%CI = 0.241-1.004，p = 0.051）具有边缘显著性。与健康对照组相比，患者的可溶性 HLA-G 水平显着升高（标准化均数差异[SMD] = 1.434，95%CI = 0.442-2.526，p = 0.005）。按癌症类型分层显示，宫颈癌（SMD = 4.889，95%CI = 0.468-9.310，p = 0.030）和亚洲血统患者（SMD = 4.889，95%CI = 0.467-9.309，p = 0.030）的 sHLA-G 水平显着升高。
HLA-G14-bp I/D 和+3142 C/G 多态性与 GC 和 HPV 相关的宫颈癌有关。此外，我们发现癌症患者的 sHLA-G 水平显着升高。这些结果为 GC 的诊断和免疫治疗的进一步研究提供了依据。
