宫颈鳞癌组织中miR-59...危型HPV感染的相关性研究_黄玺瑞.pdf

J Med Theor PracVol.36，No.3，Feb20232023年第36卷第3期医学理论与实践宫颈鳞癌组织中 mi-590-3P、FoxM1 及 Cdc25B 细胞核内蛋白水平与高危型 HPV 感染的相关性研究*基金项目:深圳市龙岗区医疗卫生科技计划项目(YLWS20140608111339661)黄玺瑞1廖艳芳1唐剑2邹伟文1任洁1宋楚莹1朱正1广东省深圳市龙岗中心医院1病理科2妇产科518000摘要目的:研究宫颈鳞癌组织中微小 NA-590-3P(mi-590-3P)、叉头盆蛋白质 M1(FoxM1)及细胞分裂周期因子25B(Cdc25B)细胞核内蛋白水平与高危型人乳头状瘤病毒(HPV)感染的相关性。方法:将 2014 年 2 月2019 年 12月医院通过宫颈活检、锥切以及子宫切除获取的宫颈组织标本 300 份纳入研究。将其分为正常组织 59 例，宫颈上皮内瘤变(CIN)1 组织62 例，CIN2/3 组织101 例，宫颈鳞癌组织78 例。采用实时荧光定量 PC 检测不同组织中的 mi-590-3P 表达水平，以免疫组织化学法检测 FoxM1、Cdc25B 蛋白表达情况，并进行23 种基因型 HPV DNA 的检测。比较不同宫颈组织中的 mi-590-3P 以及 FoxM1、Cdc25B 蛋白表达情况，高危型 HPV 感染情况，并以 Spearman 相关性分析明确宫颈鳞癌组织中的 mi-590-3P 以及 FoxM1、Cdc25B 蛋白表达情况与高危型 HPV 感染的关系。采用受试者工作特征(OC)曲线明确 mi-590-3P 以及 FoxM1、Cdc25B 蛋白诊断 CIN2+的效能。结果:CIN2/3 组织以及宫颈鳞癌组织中的 mi-590-3P 表达水平均高于正常组织、CIN1 组织，且 CIN1 组织中的 mi-590-3P 表达水平均高于正常组织(F=46 873，P=0 000);CIN2/3 组织以及宫颈鳞癌组织中的 FoxM1 蛋白阳性率及 Cdc25B 蛋白阳性率均高于正常组织及 CIN1 组织，且 CIN1 组织中的 FoxM1、Cdc25B 蛋白阳性率均高于正常组织(2=47 293、51 041，P=0 000、0 000)。CIN2/3 组织以及宫颈鳞癌组织中的高危型 HPV 感染率明显高于正常组织、CIN1 组织，且 CIN1 组织中的高危型 HPV感染率明显高于正常组织(2=67 293，P=0 000)。经 Spearman 相关性分析可得:宫颈鳞癌组织中 mi-590-3、FoxM1、Cdc25B 蛋白表达率均和高危型 HPV 感染呈正相关。经 OC 曲线分析发现:mi-590-3P 以及 FoxM1、Cdc25B蛋白联合检测诊断 CIN2+的曲线下面积、灵敏度、特异度分别为 0 884、0 90、0 88，均高于上述三项指标单独检测。结论:宫颈鳞癌组织中 mi-590-3P、FoxM1 及 Cdc25B 细胞核内蛋白水平与高危型 HPV 感染密切相关，有望成为早期诊断 CIN2+的潜在生物学指标，值得临床重点关注。关键词宫颈鳞癌mi-590-3P叉头盆蛋白质 M1细胞分裂周期因子 25B人乳头状瘤病毒中图分类号:737.33文献标识码:Adoi:10.19381/j.issn.1001-7585.2023.03.006Correlation between mi-590-3P，FoxM1 and Cdc25B Nuclear Protein Levels and High-risk HPV Infection in Cervi-cal Squamous Cell CarcinomaHUANG Xirui#，LIAO Yanfang，TANG Jian，et al.#Department of Pathology，Shenzhen Longgang Central Hospital，Shenz-hen City，Guangdong Province518000ABSTACT Objective:To investigate the correlation between mi-590-3P，FoxM1 and cell division cycle factor 25B(Cdc25B)nuclear protein levels and high-risk human papillomavirus(HPV)infection in cervical squamous cell carcinomaMethods:From February 2014 to December 2019，300 cervical tissue samples were collected from hospitals through cervicalbiopsy，cone-cutting and hysterectomy According to the difference of disease types，59 cases of normal tissue，62 cases ofcervical intraepithelial neoplasia(CIN)，101 cases of CIN2/3 of the tissue，and 78 cases of cervical squamous cell carcinomawere classified The expression levels of mi-590-3P in different tissues were detected by real-time fluorescence quantitativePC，FoxM1 and Cdc25B protein expressions were detected by immunohistochemical method，and 23 genotypes of HPV DNAwere detected The expressions of mi-590-3P，FoxM1 and Cdc25B in different cervical tissues and high-risk HPV infectionwere compared Spearman correlation analysis was used to determine the relationship between the expressions of mi-590-3P，FoxM1 and Cdc25B in cervical squamous cell carcinoma tissues and high-risk HPV infection The efficacy of mi-590-3P andFoxM1 and Cdc25B in the diagnosis of CIN2+was determined by OC curves esults:The expression levels of mi-590-3pin CIN2/3 tissues and cervical squamous cell carcinoma tissues were higher than those in normal tissues and CIN1 tissuesThe expression level of mi-590-3p in CIN1 tissues was higher than that in normal tissues(F=46 873，P=0 000)FoxM1and Cdc25B protein positive rates in CIN2/3 tissues and cervical squamous cell carcinoma tissues were higher than that in nor-mal tissues and CIN1 tissues(all P=0 000)The infection rate of high-risk HPV in CIN2/3 tissues and cervical squamous083医学理论与实践2023年第36卷第3期Vol.36，No.3，Feb2023J Med Theor Praccell carcinoma tissues were significantly higher than that in normal tissues and CIN1 tissues，and the infection rate of high-riskHPV in CIN1 tissues was significantly higher than that in normal tissues(2=67.293，P=0 000)Spearman correlation a-nalysis showed that the expression rates of mi-590-3，FOXM1 and Cdc25b in cervical squamous cell carcinoma tissues wereall positively correlated with high-risk HPV infection OC curve analysis showed that the area under the curve，sensitivity andspecificity of the combined detection of mi-590-3p，FOXM1 and Cdc25b for the diagnosis of CIN2+were 0 884，0 90 and0 88，respectively，which were all higher than those of the above three indicators detected alone Conclusion:mi-590-3P，FoxM1 and Cdc25B intracellular protein levels in cervical squamous cell carcinoma are closely related to high-risk HPV infec-tion，and are expected to be potential biological indicators for early diagnosis of CIN2+，which are worthy of clinical attentionKEY WODSCervical squamous cell carcinomami-590-3PFork head basin protein M1Cell division cycle factor25B Human papillomavirus宫颈鳞癌属于临床上较为常见的女性生殖系统恶性肿瘤之一，具有较高的发病率以及死亡率，已成为严重威胁女性生命健康安全的重大疾病之一，受到国内外的重点关注1-2。人乳头状瘤病毒(Human papillomavirus，HPV)是乳头多瘤空泡病毒科乳 头 瘤 病 毒 属，其 中 HPV16、18 属 于 高 危 型HPV，若出现持续感染，会增加宫颈癌发生的风险，亦是宫颈癌发生的关键因素之一3-4。宫颈细胞学以及高危型 HPV 检测是目前临床上用以筛查宫颈癌的重要手段，但两者均有灵敏度以及特异度相对不高的局限性。微小 NA-26a(microNA-26a，mi-590-3P)是近年来所发现的一种 miNA，可能通过靶向调控多种下游基因或(和)蛋白的表达，继而对多种肿瘤细胞的迁移以及侵袭产生影响，介导了宫颈癌的发生、发展过程5。另有免疫组织化学检测发现，叉头盆蛋白质 M1(Fork headbasin protei