Xu Hui-Hui, Zhang Xia, Zheng Hai-Hong, Han Qiu-Yue, Lin Ai-Fen, Yan Wei-Hua
1Medical Research Center, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai, Zhejiang, China.
2Laboratory of Gynecologic Oncology, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai, Zhejiang, China.
Infect Agent Cancer. 2018 Dec 29;13:42. doi: 10.1186/s13027-018-0217-2. eCollection 2018.
Human leukocyte antigen (HLA)-G is an immune checkpoint molecule, which expression in cervical cancer cells enables them to escape immunosurveillance. To date, limited information has been published on the association of HLA-G genetic background in malignant cells with levels of HLA-G expression and the clinical outcome of patients.
We investigated the influence of the HLA-G (rs66554220) and + 3142 (rs1063320) polymorphisms in 130 cases of HPV16 infection, 130 cases of HPV18 infection and 185 age-matched, unrelated, HPV-negative, and cytologically normal Chinese Han women. Case-matched cervical biopsy tissues were evaluated by immunohistochemistry.
Our findings show that the frequency of alleles, (38.5% vs 29.2%, OR = 1.52, < 0.05) and + 3142 (72.7% vs 57.0%, OR = 2.01, < 0.05), were significantly increased in the HPV18-infected group compared with the control group. The polymorphisms (alleles and + 3142) are also associated with the progression of HPV18-related cervical lesions. Moreover, HLA-G expression increased from CIN1 to CIN2/3 lesions and was highest in patients with adenocarcinoma; however, a significant association between these characteristics and the HLA-G polymorphisms was not observed.
Our results support that the and + 3142 alleles are risk factors for HPV18 infections and influence the progression of HPV18-related cervical lesions. This suggests that HLA-G-driven immune mechanisms play an important role in cervical carcinogenesis.
人类白细胞抗原（HLA）-G是一种免疫检查点分子，其在宫颈癌细胞中的表达使其能够逃避免疫监视。迄今为止，关于恶性细胞中HLA-G基因背景与HLA-G表达水平及患者临床结局之间关联的信息报道有限。
我们调查了130例HPV16感染病例、130例HPV18感染病例以及185名年龄匹配、无亲缘关系、HPV阴性且细胞学正常的中国汉族女性中HLA-G（rs66554220）和+3142（rs1063320）多态性的影响。通过免疫组织化学对病例匹配的宫颈活检组织进行评估。
我们的研究结果显示，与对照组相比，HPV18感染组中 （38.5%对29.2%，OR = 1.52，<0.05）和+3142（72.7%对57.0%，OR = 2.01，<0.05）等位基因的频率显著增加。 多态性（等位基因 和+3142）也与HPV18相关宫颈病变的进展有关。此外，HLA-G表达从CIN1病变到CIN2/3病变增加，在腺癌患者中最高；然而，未观察到这些特征与HLA-G多态性之间存在显著关联。
我们的结果支持 和+3142等位基因是HPV18感染的危险因素，并影响HPV18相关宫颈病变的进展。这表明HLA-G驱动的免疫机制在宫颈癌发生中起重要作用。
