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. 2018 Dec 29:13:42.
doi: 10.1186/s13027-018-0217-2. eCollection 2018.

Association of HLA-G 3' UTR polymorphism and expression with the progression of cervical lesions in human papillomavirus 18 infections

Hui-Hui Xu  1   2 , Xia Zhang  3 , Hai-Hong Zheng  4 , Qiu-Yue Han  3 , Ai-Fen Lin  3 , Wei-Hua Yan  1   2
Affiliations

Association of HLA-G 3' UTR polymorphism and expression with the progression of cervical lesions in human papillomavirus 18 infections

Hui-Hui Xu et al. Infect Agent Cancer. .

Abstract

Background: 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.

Methods: We investigated the influence of the HLA-G 14 bp In/Del (rs66554220) and + 3142C/G (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.

Results: Our findings show that the frequency of alleles, 14 bp In (38.5% vs 29.2%, OR = 1.52, P < 0.05) and + 3142G (72.7% vs 57.0%, OR = 2.01, P < 0.05), were significantly increased in the HPV18-infected group compared with the control group. The HLA-G polymorphisms (alleles 14 bp In and + 3142G) 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.

Conclusion: Our results support that the HLA-G 14 bp In and + 3142G 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.

Keywords: Cervical cancer; Expression; Human leukocyte antigen-G; Human papillomavirus 18; Polymorphism; Precancerous cervical lesions.

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Conflict of interest statement

We all agreed to submit our manuscript “Association of HLA-G 3′ UTR polymorphism and expression with the progression of cervical lesions in human papillomavirus 18 infections” to Infectious Agents and Cancer. This manuscript has not been submitted to elsewhere.The authors declare no conflict of interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Immunohistochemical staining of HLA-G expression in cervical lesions. (a) normal cervical tissue. The arrow refer to HPV hollowed out cells; (b) CIN1 lesion. The arrow refer to basal cells of the epithelium; (c) CIN2 lesion; (d) CIN3 lesion. Squamous cell abnormalities involving glands; (e) Adenocarcinoma. HLA-G protein is diffusely expressed in cytoplasm and membrane. Positive for HLA-G expression increased from CIN1 to CIN2/3 lesions and was highest in ADC lesions
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References

    1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108. doi: 10.3322/caac.21262. - DOI - PubMed
    1. Crosbie EJ, Einstein MH, Franceschi S, Kitchener HC. Human papillomavirus and cervical cancer. Lancet. 2013;382:889–899. doi: 10.1016/S0140-6736(13)60022-7. - DOI - PubMed
    1. Sasagawa T, Takagi H, Makinoda S. Immune responses against human papillomavirus (HPV) infection and evasion of host defense in cervical cancer. J Infect Chemother. 2012;18:807–815. doi: 10.1007/s10156-012-0485-5. - DOI - PubMed
    1. Carosella ED, HoWangYin KY, Favier B, LeMaoult J. HLA-G-dependent suppressor cells: diverse by nature, function, and significance. Hum Immunol. 2008;69:700–707. doi: 10.1016/j.humimm.2008.08.280. - DOI - PubMed
    1. Yan WH. HLA-G Expression in Cancers: Potential Role in Diagnosis, Prognosis and Therapy. Endocr Metab Immune Disord Drug Targets. 2011;11:76–89. doi: 10.2174/187153011794982059. - DOI - PubMed