高危型HPV感染状况、血清PTX3、TFF1表达与宫颈癌病变程度的相关性研究

Study on the correlation between high-risk HPV infection, serum PTX3 and TFF1 expression, and the severity of cervical cancer lesions

摘要

目的 分析宫颈癌患者高危型人乳头瘤病毒(HPV)感染状况、血清正五聚蛋白3(PTX3)及三叶因子1(TFF1)的水平及其与宫颈癌病变程度的相关性.方法 选择2021年6月至2023年6月在本院收治的360例高级别宫颈上皮内瘤变(HSIL)患者作为研究对象,根据最终诊断结果,将其分为宫颈癌组(n=175)和宫颈上皮内瘤变(CIN)组(n=185),另选取同期体检健康女性160例作为对照组.比较各组高危HPV感染情况、血清PTX3及TFF1的水平及其与宫颈癌病变程度的相关性.结果 CINⅢ组患者的高危HPV感染率(73.68%)显著高于对照组参与者(0.00%)及CINⅠ组患者(35.29%)(P<0.05);宫颈癌国际妇产科联盟(FIGO)ⅠB期组和宫颈癌FIGO ⅡA期组患者高危HPV感染率(分别为87.87%和92.66%)均显著高于对照组参与者(0.00%)、CINⅠ组患者(35.29%)、CINⅡ组患者(60.47%)和CINⅢ组患者(73.68%)(P<0.05).对照组、CIN组及宫颈癌组患者之间血清PTX3和TFF1水平比较,差异具有统计学意义(F值分别为180.087、175.767,P<0.05).不同CIN病变血清PTX3、TFF1水平比较,差异有统计学意义(F值分别为57.381、73.891,P<0.05).FIGOⅡA期、有淋巴结转移的宫颈癌患者血清PTX3、TFF1水平显著高于FIGOⅠB期、无淋巴结转移的患者(t值分别为7.262、6.429以及8.107、5.587,P<0.05);随着HPV病毒负荷量分级的增加,宫颈癌患者血清PTX3、TFF1水平显著上升(F值分别为88.169、85.550,P<0.05);宫颈癌患者肿瘤分化程度越低,其血清PTX3、TFF1水平越高(F值分别为110.194、111.731,P<0.05).结论 高危型HPV感染率、血清PTX3、TFF1水平升高与宫颈癌病变程度密切相关,临床上及时监测高危型HPV感染状况及血清PTX3、TFF1水平变化,可辅助评估宫颈癌的发生风险.

Abstract

Objective To analyze the status of high-risk human papillomavirus (HPV) infection, serum pentraxin 3 (PTX3), and trefoil factor 1 (TFF1) levels in cervical cancer patients and their correlation with the severity of cervical cancer lesions. Methods A total of 360 patients with high-grade squamous intraepithelial lesions (HSIL) who were admitted to our hospital from June 2021 to June 2023 were selected as the study subjects. Based on the final diagnosis, they were divided into a cervical cancer group (n=175) and a cervical intraepithelial neoplasia (CIN) group (n=185). Additionally, 160 healthy women undergoing physical examinations during the same period were selected as the control group. The high-risk HPV infection status, serum PTX3 and TFF1 levels, and their correlation with the severity of cervical cancer lesions were compared among the groups. Results The high-risk HPV infection rate in the CIN Ⅲ group (73.68%) was significantly higher than that in the control group (0.00%) and the CIN Ⅰ group (35.29%) (P<0.05). The high-risk HPV infection rates in the FIGO stage ⅠB (87.87%) and FIGO stage ⅡA cervical cancer groups (92.66%) were significantly higher than those in the control group (0.00%), CIN Ⅰ group (35.29%), CIN Ⅱ group (60.47%), and CIN Ⅲ group (73.68%) (P<0.05). There were statistically significant differences in serum PTX3 and TFF1 levels among the control, CIN, and cervical cancer groups (F=180.087 and 175.767, respectively, P<0.05). The differences in serum PTX3 and TFF1 levels among different CIN lesions were also statistically significant (F=57.381 and 73.891, respectively, P<0.05). Patients with FIGO stage ⅡA cervical cancer and those with lymph node metastasis had significantly higher serum PTX3 and TFF1 levels than patients with FIGO stage ⅠB cervical cancer and those without lymph node metastasis (t=7.262, 6.429, 8.107, and 5.587, respectively, P<0.05). As the HPV viral load increased, serum PTX3 and TFF1 levels in cervical cancer patients showed a significant upward trend (F=88.169 and 85.550, respectively, P<0.05). Additionally, lower tumor differentiation in cervical cancer patients was associated with higher serum PTX3 and TFF1 levels (F=110.194 and 111.731, respectively, P<0.05). Conclusion The increased high-risk HPV infection rate and elevated serum PTX3 and TFF1 levels are closely associated with the severity of cervical cancer lesions. Clinically, timely monitoring of high-risk HPV infection status and changes in serum PTX3 and TFF1 levels may help assess the risk of cervical cancer development.

关键词

宫颈癌 / 宫颈上皮内瘤变 / 高危型人乳头瘤病毒 / 正五聚蛋白3 / 三叶因子1

Key words

cervical cancer / cervical intraepithelial neoplasia / high risk human papillomavirus / pentraxin-3 / trefoil factor family 1

参考文献

[1] 阮俊霞, 王成群, 杨柏柳. 宫颈癌组织中MiR-1287-5p、HOXA7表达及临床意义[J]. 中国计划生育学杂志, 2023, 31(2): 424-428.

[2] 周飞, 何江耀, 夏丽丽, 等. HBV与HPV对宫颈上皮内病变及宫颈癌影响[J]. 中国实验诊断学, 2023, 27(5): 542-545.

[3] 孙珍, 郭夏娜. sICOS和sPD-1在HR-HPV感染、CIN及宫颈癌中的表达及临床意义[J]. 医学理论与实践, 2023, 36(8): 1272-1275.

[4] Berggrund M, Enroth S, Lundberg M, et al. Identification of candidate plasma protein biomarkers for cervical cancer using the multiplex proximity extension assay[J]. Mol Cell Proteomics, 2019, 18(4): 735-743.

[5] 刘继玉. 血清TFF1、CA153检测在乳腺癌诊断中的应用价值[J]. 中国医学创新, 2022, 19(4): 179-182.

[6] 艾克热木·玉苏甫, 王海江, 帕尔哈提·沙依木, 等. TFF1和TFF3在结直肠癌中的表达与临床病理特点及预后的关系[J]. 中国肿瘤临床, 2014, 41(6): 381-385.

[7] 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.

[8] 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.

[9] Gaffney D K, Hashibe M, Kepka D, et al. Too many women are dying from cervix cancer: problems and solutions[J]. Gynecol Oncol, 2018, 151(3): 547-554.

[10] 薛宏, 汪光慧, 陈猛, 等. 腹腔镜下保留盆腔自主神经广泛性子宫切除术治疗早期宫颈癌患者的疗效研究[J]. 中国现代医学杂志, 2023, 33(3): 19-25.

[11] Tsu V, Jeronimo J. Saving the world's women from cervical cancer[J]. N Engl J Med, 2016, 374(26): 2509-2511.

[12] 师晓艳, 雷侠. 宫颈液基细胞学检查与高危型HPV检测用于宫颈癌前病变并发感染早期筛查的对比研究[J]. 中国性科学, 2017, 26(1): 33-35.

[13] 尤小燕, 王雅莉, 刘文枝, 等. 高危型HPV联合细胞学检测在宫颈癌及癌前病变筛查中临床意义[J]. 实用预防医学, 2017, 24(8): 986-988.

[14] 柯善英, 刘庆. Th1/Th2细胞因子在不同宫颈上皮内瘤变程度及宫颈癌患者血清中的表达水平及其临床意义[J]. 医学临床研究, 2023, 40(2): 287-289.

[15] Zhang H, Wang Y, Zhao Y, et al. PTX3 mediates the infiltration, migration, and inflammation-resolving-polarization of macrophages in glioblastoma[J]. CNS Neurosci Ther, 2022, 28(11): 1748-1766.

[16] Giacomini A, Ghedini G C, Presta M, et al. Long pentraxin 3: a novel multifaceted player in cancer[J]. Biochim Biophys Acta Rev Cancer, 2018, 1869(1): 53-63.

[17] Ying T H, Lee C H, Chiou H L, et al. Knockdown of pentraxin 3 suppress tumorigenicity and metastasis of human cervical cancer cells[J]. Sci Rep, 2016, 6: 29385.

[18] 王蒙, 马涛, 刘庆东, 等. 血清生长激素释放多肽和三叶因子1与胃溃疡病理特征及预后的关系[J]. 中国医刊, 2023, 58(1): 50-54.

[19] 李亚光, 邓同兴, 赵克芳, 等. 稳定过表达TFF1对MHCC97H细胞增殖、侵袭、转移及EMT发生的影响[J]. 中国免疫学杂志, 2021, 37(14): 1733-1737.

[20] Xue F, Meng Y, Jiang J. Diagnostic value of dynamic enhanced magnetic resonance imaging combined with serum CA15-3, CYFRA21-1, and TFF1 for breast cancer[J]. J Healthc Eng, 2022, 2022: 7984591-7984597.

[21] Okuda Y, Shimura T, Abe Y, et al. Urinary dipeptidase 1 and trefoil factor 1 are promising biomarkers for early diagnosis of colorectal cancer[J]. J Gastroenterol, 2024, 59(7): 572-585.

[22] 何盛银, 刘孝德, 赵攀, 等. 三叶肽因子在膀胱癌中的表达及临床意义[J]. 中华泌尿外科杂志, 2018, 39(2): 103-108.

[23] 胡玉海, 余婷, 王晶. 血清TFF1、CA153检测在乳腺癌诊断中的应用价值[J]. 国际检验医学杂志, 2021, 42(2): 210-213.

[24] Hasebe K, Yamazaki K, Yamaguchi J, et al. Trefoil factor 1 inhibits the development of esophageal adenocarcinoma from Barrett's epithelium[J]. Lab Invest, 2022, 102(8): 885-895.

基金资助

衡水市科技计划项目(2023014059Z)