宫颈癌及癌前病变患者高危型人乳头瘤病毒感染现状分析及与血清人白细胞抗原-G、高迁移率族蛋白A1、转化生长因子-β1表达水平的相关性研究

doi:10.19871/j.cnki.xfcrbzz.2025.01.012

摘要/Abstract

摘要： 目的探究宫颈癌及癌前病变患者高危型人乳头瘤病毒（high-risk human papillomavirus,HR-HPV）感染现状及与血清人白细胞抗原-G（human leukocyte antigen-G,HLA-G）、高迁移率族蛋白A1（high mobility group protein A1,HMGA1）及转化生长因子-β1（transforming growth factor-β1,TGF-β1）表达水平的相关性。方法选取2023年3月至2024年3月于重庆市开州区中医院接受治疗的148例宫颈癌患者,将其设为宫颈癌组,另选取同时期于医院接受治疗的92例宫颈上皮内瘤变（cervical intraepithelial neoplasias,CIN）患者,以及行健康体检的80例正常女性,分别将其设为癌前病变组和对照组。观察两组患者HR-HPV感染情况,以及三组受试者血清HLA-G、HMGA1、TGF-β1水平,同时分析血清HLA-G、HMGA1、TGF-β1水平与宫颈癌患者HR-HPV感染的相关性。结果癌前病变组中CIN Ⅲ级HR-HPV感染率较CINⅠ级更高（χ²=11.642,P=0.001）,宫颈癌组子宫内膜癌的国际妇产科联盟（international federation of gynecology and obstetrics,FIGO）ⅠB期和FIGOⅡA期HR-HPV感染率均高于CINⅠ级、CINⅡ级和CIN Ⅲ级（Z=22.045,Z=51.391,均P<0.001）;宫颈癌组HR-HPV感染患者血清HLA-G、HMGA1、TGF-β1水平较非HR-HPV感染患者明显增高,癌前病变组HR-HPV感染患者血清HLA-G、HMGA1、TGF-β1水平高于非HR-HPV感染患者,差异均具有统计学意义（P<0.05）。宫颈癌组患者血清HLA-G、HMGA1、TGF-β1水平显著高于癌前病变组与对照组,癌前病变组患者血清HLA-G、HMGA1、TGF-β1水平高于对照组（P<0.05）;通过Pearson相关系数分析得出,血清HLA-G、HMGA1、TGF-β1水平与宫颈癌患者HR-HPV感染均呈正相关（r=0.385,P<0.001;r=0.376, P<0.001;r=0.431,P<0.001）。结论宫颈癌与癌前病变患者HR-HPV感染率随病情进展升高,血清HLA-G、HMGA1、TGF-β1水平显著上调,且与HR-HPV感染密切相关,为宫颈癌的早期诊断等提供了新的生物标志物。

关键词: 宫颈癌, 癌前病变, 高危型人乳头瘤病毒, 感染, 人白细胞抗原-G, 高迁移率族蛋白A1, 转化生长因子-β1, 相关性

Abstract: Objective To explore the infection status of high-risk human papillomavirus (HR-HPV) in patients with cervical cancer and precancerous lesions and its relationship with serum human leukocyte antigen-G, Correlation between HLA-G, high mobility group protein A1 (HMGA1) and transforming growth factor-β 1 (TGF-β 1). Method A total of 148 cervical cancer patients treated in Chongqing Kaizhou District Traditional Chinese Medicine Hospital from March 2023 to March 2024 were selected as the cervical cancer group. Additionally, 92 cervical intraepithelial neoplasia (CIN) patients treated during the same period and 80 healthy females undergoing routine health examinations in our hospital were designated as the precancerous lesion group and the control group, respectively. Serum levels of HLA-G, HMGA1, TGF-β 1, and HR-HPV infection status were examined in all three groups. The HR-HPV infection rates and serum levels of HLA-G, HMGA1, and TGF-β 1 were observed and analyzed for their correlation with HR-HPV infection in cervical cancer patients. Result The infection rate of HR-HPV in CINⅢ was higher than CINⅠ in precancerous lesion group (χ²=11.642, P=0.001), and the infection rate of HR-HPV in FIGOⅠB and FIGOⅡA are all higher than CINⅠ, CINⅡ and CINⅢ in cervical cancer group (Z=38.566, Z=51.391, P<0.001). By comparison, the serum levels of HLA-G, HMGA1 and TGF-β 1 in patients with HPV infection in cervical cancer group were significantly higher than those in patients without HPV infection, and the serum levels of HLA-G, HMGA1 and TGF-β 1 in patients with HPV infection in precancerous lesions group were higher than those in patients without HPV infection, and the differences were statistically significant (P<0.05). The results showed that the serum levels of HLA-G, HMGA1 and TGF-β 1 in cervical cancer group were significantly higher than those in precancerous lesion group and control group, and the serum levels of HLA-G, HMGA1 and TGF-β 1 in precancerous lesion group were higher than those in control group (P<0.05). Pearson correlation analysis showed that the serum levels of HLA-G, HMGA1 and TGF-β 1 were positively correlated with HR-HPV infection in patients with cervical cancer (r=0.385, P<0.001; r=0.376,P<0.001; r=0.431, P<0.001）. Conclusion The HR-HPV infection rate in 11 patients with cervical cancer increases with the progression of the disease, and the serum levels of HLA-G, HMGA1 and TGF-β 1 are significantly up-regulated, which is closely related to HR-HPV infection, providing a new biomarker for the early diagnosis of cervical cancer.

Key words: Cervical cancer, Precancerous lesions, High-risk human papillomavirus, Infection, Human leukocyte antigen-G, High mobility group protein A1, Transforming growth factor-β 1, Correlation

中图分类号:

R737.3

黄义萍, 陈素平, 薛高峰. 宫颈癌及癌前病变患者高危型人乳头瘤病毒感染现状分析及与血清人白细胞抗原-G、高迁移率族蛋白A1、转化生长因子-β1表达水平的相关性研究[J]. 新发传染病电子杂志, 2025, 10(1): 62-67.

Huang Yiping, Chen Suping, Xue Gaofeng. Analysis of high-risk human papillomavirus infection in patients with cervical cancer and precancerous lesions and its correlation with serum human leukocyte antigen-G, high mobility group protein A1 and transforming growth factor-β 1 expression levels[J]. Electronic Journal of Emerging Infectious Diseases, 2025, 10(1): 62-67.

参考文献

[1] 王丽萍, 张月, 孙滨州, 等. 120例女性宫颈病变患者HPV感染的基因型分布和病理特征分析[J/CD].新发传染病电子杂志, 2024, 9(4): 23-28.
[2] PALMER TJ, KAVANAGH K, CUSCHIERI K, et al.Invasive cervical cancer incidence following bivalent human papillomavirus vaccination: a population-based observational study of age at immunization, dose, and deprivation[J].J Natl Cancer Inst, 2024, 116(6): 857-865.
[3] JHA AK, MITHUN S, SHERKHANE UB, et al.Systematic review and meta-analysis of prediction models used in cervical cancer[J].Artif Intell Med,2023,139(6):102549.
[4] 王巧祎, 赵希芹, 郭雨辰, 等. HPV52 E6和E7基因多态性与宫颈上皮内瘤变相关性[J].青岛大学学报(医学版), 2022, 58(5): 667-671.
[5] 张莹, 曾妍茗, 鲁雁秋, 等. 人乳头瘤病毒疫苗接种预防感染及相关癌症的研究进展[J/CD].新发传染病电子杂志, 2023, 8(6): 84-88.
[6] 万章彩, 杨洁, 陈坤菊, 等. 中期宫颈癌患者术后血清Chemerin,Hmga1水平变化及对2年内复发的影响[J].中国性科学, 2023, 32(12): 90-94.
[7] 史中娜, 王宝金, 白杨, 等. 高危HPV载量与血清FSTL1,TGF-β1水平联合检测对宫颈病变的预测价值[J].中国卫生检验杂志, 2023, 33(16): 2008-2011.
[8] 李静, 索红燕, 孔为民. 《国际妇产科联盟(FIGO)2018癌症报告:宫颈癌新分期及诊治指南》解读[J].中国临床医生杂志, 2019, 47(6): 646-649.
[9] 茅娅男, 尤志学. ASCCP 2019共识指南子宫颈癌前病变管理解读[J].现代妇产科进展, 2020, 29(12): 936-941.
[10] LEI J, ARROYO-MÜHR LS, LAGHEDEN C, et al. Human Papillomavirus Infection Determines Prognosis in Cervical Cancer[J].J Clin Oncol, 2022, 40(14): 1522-1528.
[11] SINGINI MG, SINGH E, BRADSHAW D, et al.Usefulness of high-risk HPV early oncoprotein (E6 and E7) serological markers in the detection of cervical cancer: A systematic review and meta-analysis[J].J Med Virol, 2023, 95(1): e27900.
[12] BHATTACHARJEE R, DAS SS, BISWAL SS, et al.Mechanistic role of HPV-associated early proteins in cervical cancer: Molecular pathways and targeted therapeutic strategies[J].Crit Rev Oncol Hematol, 2022, 174(6): 103675.
[13] 杜靖, 李晨, 王晓静, 等.白介素-2和信号转导和转录激活因子5在宫颈病变患者血清,宫颈组织和细胞中的表达及意义[J].新乡医学院学报, 2022, 39(10): 934-941.
[14] GAN J, DI XH, YAN ZY, et al.HLA-G 3'UTR polymorphism diplotypes and soluble HLA-G plasma levels impact cervical cancer susceptibility and prognosis[J].Front Immunol, 2022, 13(3): 1076040.
[15] HE Z, JING X, DAI X, et al.The Ability of Clinically Relevant Chemotherapeutics to Induce Immunogenic Cell Death in Squamous Cell Carcinoma[J].Front Biosci (Landmark Ed), 2024, 29(4): 158.
[16] LIU P, PEI JJ, LI L, et al.Sildenafil Inhibits the Growth and Epithelial-to-mesenchymal Transition of Cervical Cancer via the TGF-β1/Smad2/3 Pathway[J].Curr Cancer Drug Targets, 2023, 23(2): 145-158.
[17] BOWDEN SJ, DOULGERAKI T, BOURAS E, et al.Risk factors for human papillomavirus infection, cervical intraepithelial neoplasia and cervical cancer: an umbrella review and follow-up Mendelian randomisation studies[J].BMC Med, 2023, 21(1): 274.
[18] XU HH, XIE YY, JUN-GAN, et al.Dynamic changes of soluble HLA-G and cytokine plasma levels in cervical cancer patients: potential role in cancer progression and immunotherapy[J].J Cancer Res Clin Oncol, 2023, 149(8): 4195-4204.
[19] 徐菁华, 李吉. SPP1与PI3K在宫颈癌细胞中的表达及临床意义[J].药物生物技术, 2024, 31(2): 171-174.
[20] 陈丽艳, 姜继勇, 刘莎, 等. 宫颈癌患者高危型HPV感染状况及与血清HLA-G、TGF-β1表达的相关性[J].临床和实验医学杂志, 2022, 21(3): 295-299.