HPV16感染与宫颈鳞癌的相关性及对Wnt/β-catenin信号转导通路表达的影响

Correlation of HPV16 Infection and Cervical Squamous Cancer and Its Influence on the Expression of Wnt/β-catenin Signal Transduction Pathways

目的探究人乳头瘤病毒16(HPV16)感染与宫颈鳞癌(SCC)的相关性及对Wnt/β-catenin信号转导通路表达的影响。方法收集手术切除获得的106例SCC组织、76例宫颈上皮瘤变(CIN)组织和54例正常宫颈组织,采用荧光定量PCR及免疫组化法检测各组HPV16感染及宫颈组织中Wnt-3a、β-catenin蛋白表达情况,分析HPV16感染与Wnt-3a、β-catenin蛋白表达关系。结果Wnt-3a蛋白在各宫颈组织中均表达在胞质;而β-catenin蛋白在正常宫颈组织中表达在细胞膜,在CIN组织和SCC组织中主要异常表达在胞质和胞核。HPV16感染率、Wnt-3a、β-catenin蛋白阳性表达率在各组织中比较存在显著差异(P<0.05);FIGO分期Ⅱ期、中低分化、淋巴结转移患者HPV16感染率分别高于FIGO分期Ⅰ期、高分化、淋巴结未转移患者(P<0.05);FIGO分期Ⅱ期、中低分化患者Wnt-3a、β-catenin蛋白阳性表达率分别高于FIGO分期Ⅰ期、高分化患者(P<0.05)。Pearson相关性分析显示,HPV16感染与宫颈鳞癌分化程度、FIGO分期、淋巴结转移、Wnt-3a、β-catenin表达呈正相关(γ>0,P<0.05),Wnt-3a、β-catenin与宫颈鳞癌分化程度、FIGO分期与呈正相关(γ>0,P<0.05)。结论HPV16与SCC临床病理具有一定相关性,还可能通过影响Wnt/β-catenin信号通路蛋白表达从而发挥促癌作用。

Objective To investigate the correlation of HPV papillomavirus 16(HPV16)infection with cervical squamous carcinoma(SCC)and the effect on the expression of Wnt/β-catenin signaling transduction pathway.Methods We collected 106 cases of SCC,cervical epithelial neoplasia(CIN)tissues and 54 normal cervical tissues through surgical resection.The expression of Wnt-3a andβ-catenin protein in HPV16 infection and cervical tissues of each group was detected by fluorescence quantitative PCR and immunohistochemistry,and the relationship between HPV16 infection and Wnt-3a andβ-catenin protein expression was analyzed.Results Wnt-3a protein was expressed in cytoplasma in all cervical tissue,while theβ-catenin protein was expressed in the cell membrane in normal cervical tissue,and major abnormal expression in CIN and SCC tissues were in cytoplasma and nuclei.The rate of HPV16 infection and Wnt-3a,β-catenin protein-positive expression rate differed significantly in various tissues(P<0.05).The prevalence of HPV16 infection was higher in patients with FIGO stageⅡ,moderately and poorly differentiated,and lymph node metastasis than in patients with FIGO stageⅠ,well differentiated,and lymph node non-metastasis,respectively(P<0.05).The positive expression rates of Wnt-3a andβ-catenin protein in FIGO stageⅡand moderately and poorly differentiated patients were higher than those in FIGO stageⅠand well differentiated patients,respectively(P<0.05).Pearson correlation analysis showed that HPV16 infection was positively correlated with cervical squamous cell carcinoma differentiation,FIGO stage,lymph node metastasis,and Wnt-3a andβ-catenin expression(γ>0,P<0.05),while Wnt-3a andβ-catenin were positively correlated with differentiation and FIGO stage of cervical squamous cell carcinoma(γ>0,P<0.05).Conclusion HPV16 has some correlation with SCC clinicopathology and may also play a role in cancer induction by affecting Wnt/β-catenin signaling pathway protein expression.