尖锐湿疣患者组织中P16INK4A、ZnT1的表达及其与HPV感染和预后的关系

Expression of P16INK4A and ZnT1 in tissues of patients with condyloma acuminatum and their relationship with HPV infection and prognosis

目的探讨尖锐湿疣(CA)患者组织中P16INK4A蛋白、锌离子转运体1(ZnT1)mRNA表达水平及其与人乳头瘤病毒(HPV)感染的关系。方法选取2019年5月至2022年5月在该院就诊的82例CA患者作为CA组,另选取同期在该院进行包皮环切术或外阴整形术的64名皮肤健康者作为对照组。收集CA组疣体组织及对照组的正常包皮或外阴组织,采用聚合酶链反应(PCR)-反向点杂交技术进行HPV分型检测,比较CA组与对照组,以及不同HPV分型CA患者P16INK4A与ZnT1 mRNA表达水平。所有CA患者均随访治疗8个月,复发的患者纳入复发组,未复发的患者纳入未复发组,比较两组P16INK4A与ZnT1 mRNA表达水平。绘制受试者工作特征(ROC)曲线分析P16INK4A、ZnT1单独及2项指标联合检测对CA预后复发的预测价值。结果82例CA患者中,27例为低危型感染(32.93%),25例为高危型感染(30.49%),30例为混合型感染(36.59%),感染HPV亚型包括6、11、16、18、31和51。CA组P16INK4A、ZnT1表达水平明显高于对照组,差异均有统计学意义(P<0.05)。P16INK4A高表达组45例、低表达组37例;ZnT1高表达组43例、低表达组39例。P16INK4A mRNA低表达组与高表达组年龄、性别、疣体数量、疣体位置比较,差异均无统计学意义(P>0.05),疣体直径、病程、HPV分型比较,差异均有统计学意义(P<0.05)。ZnT1 mRNA低表达组与高表达组年龄、性别、疣体数量、疣体位置比较,差异均无统计学意义(P>0.05),疣体直径、病程、HPV分型比较,差异均有统计学意义(P<0.05)。混合型、高危型P16INK4A、ZnT1 mRNA表达水平明显高于低危型,差异均有统计学意义(P<0.05);高危型P16INK4A、ZnT1 mRNA表达水平明显高于混合型,差异均有统计学意义(P<0.05)。CA患者随访8个月后,有29例复发(复发组),53例未复发(未复发组)。复发组P16INK4A、ZnT1 mRNA表达水平明显高于未复发组,差异均有统计学意义(P<0.05)。ROC曲线分析结果显示,P16INK4A、ZnT1 mRNA单独及2项指标联合检测预测CA预后复发的曲线下面积(AUC)分别为0.840、0.880、0.963,P16INK4A与ZnT1 mRNA联合检测预测CA预后复发的AUC大于2项指标单独检测(Z_(二者联合-P16INK4A)=2.097,P=0.036;Z_(二者联合-ZnT1)=2.074,P=0.038)。结论CA患者疣体组织中P16INK4A、ZnT1 mRNA表达水平明显升高,其表达水平与HPV感染密切相关。

Objective To investigate the expression of P16INK4A protein and zinc transporter 1(ZnT1)mRNA in tissues of condyloma acuminatum(CA)patients and their relationship with human papillomavirus(HPV)infection.Methods A total of 82 patients with CA who were treated in the hospital from May 2019 to May 2022 were selected as the CA group,and 64 healthy people with healthy skin who underwent circumcision or vulvoplasty in the hospital during the same period were selected as the control group.Collection CA group wart body organization and the control group of normal prepuce or genital tissue,using polymerase chain reaction(PCR)and reverse dot hybridization technology is used to detect the HPV types,CA group compared with control group,and different HPV types in patients with CA p16 and ZnT1 mRNA expression level.After 8 months of follow-up,the patients with recurrence were included in the recurrence group,and the patients without recurrence were included in the non-recurrence group,and the expression levels of P16INK4A and ZnT1 mRNA were compared between the two groups.The receiver operating characteristic(ROC)curve was drawn to analyze the predictive value of P16INK4A,ZnT1 alone and combined detection of the two indicators for the prognosis and recurrence of CA.Results Among the 82 CA patients,27 cases were infected with low-risk HPV(32.93%),25 cases were infected with high-risk HPV(30.49%),and 30 cases were infected with mixed HPV(36.59%).The infection subtypes included HPV 6,11,18,16,31 and 51.The expression levels of P16INK4A and ZnT1 in CA group were significantly higher than those in control group(P<0.05).There were 45 cases with high P16INK4A expression and 37 cases with low p16INK4a expression.There were 43 cases in ZnT1 high expression group and 39 cases in ZnT1 low expression group.There was no significant difference in age,gender,number and location of warts between P16INK4A mRNA low expression group and high expression group(P>0.05),but there were significant differences in the maximum diameter of warts,disease duration,and HPV typing between the two groups(P<0.05).There was no significant difference in age,gender,number and location of warts between ZnT1 mRNA low expression group and high expression group(P>0.05).There were significant differences in the maximum diameter of warts,disease duration,and HPV typing between ZnT1 mRNA low expression group and high expression group(P<0.05).The mRNA expression levels of P16INK4A and ZnT1 in the mixed type and high-risk type were significantly higher than those in the low-risk type(P<0.05).The mRNA expression levels of P16INK4A and ZnT1 in high-risk type were significantly higher than those in mixed type(P<0.05).After 8 months of follow-up,29 CA patients had recurrence and were included in the recurrence group,and 53 CA patients without recurrence were included in the non-recurrence group.The mRNA expression levels of P16INK4A and ZnT1 in the recurrence group were significantly higher than those in the non-recurrence group,and the differences were statistically significant(P<0.05).ROC curve analysis showed that the area under the curve(AUC)of P16INK4A,ZnT1 mRNA expression levels alone and the combination of the two indicators to predict the prognosis and recurrence of CA were 0.840,0.880 and 0.963 respectively.The AUC of combined detection of P16INK4A and ZnT1 mRNA in predicting the prognosis and recurrence of CA was greater than that of the two indicators alone(Z_(combined-P16INK4A)=2.097,P=0.036,Z_(combined-ZnT1)=2.074,P=0.038).Conclusion P16 in CA patients wart body organization,ZnT1 mRNA expression level increased significantly,its expression level is closely related to HPV infection.