HPVE2/E6、CDCP1、RASSF2A甲基化水平与局部免疫、HR-HPV持续感染的关系

HPV E2/E6,CDCP1,RASSF2A methylation level and its relationship with local immunity and HR-HPV persistent infection

目的探讨人乳头瘤病毒(HPV)E2/E6、含CUB结构域蛋白1(CDCP1)、RAS相关结构域蛋白2A基因(RASSF2A)甲基化水平与宫颈病变级别、局部免疫的关联性。方法选取2018年1月至2020年6月海口市妇幼保健院诊治的158例高危型HPV(HR-HPV)感染患者作为研究对象。比较不同宫颈病变级别患者HPVE2/E6、CDCP1、RASSF2A甲基化水平,并给予重组人干扰素治疗,根据治疗效果分为转阴组(n=132)、持续感染组(n=26),比较两组HPVE2/E6、CDCP1mRNA、RASSF2AmRNA、局部免疫功能水平及其相关性,探讨HR-HPV持续感染影响因素,评估上述指标预测HR-HPV持续感染的效能。结果高级别宫颈上皮内病变(HSIL)患者CDCP1阳性率、RASSF2AmRNA、CDCP1mRNA高于无宫颈上皮内病变(NSIL)、低级别宫颈上皮内病变(LSIL)患者,HPVE2/E6、RASSF2AmRNA低于NSIL、LSIL患者(P<0.05)。HPVE2/E6、RASSF2AmRNA与CD4^(+)呈正相关,与CD8^(+)呈负相关;CDCP1mRNA与CD4^(+)呈负相关,与CD8^(+)呈正相关(P<0.05);HPVE2/E6、CDCP1mRNA、RASSF2AmRNA是HR-HPV持续感染的重要影响因素(P<0.05);HPVE2/E6+CDCP1mRNA+RASSF2AmRNA预测HR-HPV持续感染的AUC最大,为0.887。结论HPVE2/E6、CDCP1、RASSF2A甲基化水平与宫颈病变级别、局部免疫密切相关,联合应用对临床预测HR-HPV持续感染、评估宫颈病变级别、预防宫颈癌变发生具有较高的临床应用价值。

Objective To investigate the relationship between the methylation levels of Human papillomavirus(HPV)E2/E6,CUB domain-containing protein 1(CDCP1),RAS associated domain family 2 A gene(RASSF2 A)and cervical lesion grade and local immunity.Methods 158 patients with high-risk HPV(HR-HPV)infection in Haikou Maternal and Child Health Care Hospital from January 2018 to June 2020 were selected as the study subjects.The methylation levels of HPV E2/E6,CDCP1 and RASSF2 A in patients with different grades of cervical lesions were compared,and the patients were treated with recombinant human interferon.According to the therapeutic effect,the patients were divided into negative group(n=132)and persistent infection group(n=26).The levels of HPV E2/E6,CDCP1 mRNA,RASSF2 A mRNA and local immune function and their correlation were compared between the two groups,to explore the influencing factors of HR-HPV persistent infection,and to evaluate the efficacy of these indicators in predicting HR-HPV persistent infection.Results The positive rate of CDCP1,RASSF2 A and CDCP1 mRNA in HSIL patients were higher than those in NSIL and LSIL patients,and HPV E2/E6 and RASSF2 A mRNA were lower than those in NSIL and LSIL patients(P<0.05).HPV E2/E6 and RASSF2 A mRNA were positively correlated with CD4^(+)and negatively correlated with CD8^(+).CDCP1 mRNA was negatively correlated with CD4^(+)and positively correlated with CD8^(+)(P<0.05).HPV E2/E6,CDCP1 mRNA and RASSF2 A mRNA were important influencing factors for persistent HR-HPV infection(P<0.05).The AUC of persistent HR-HPV infection predicted by HPV E2/E6+CDCP1 mRNA+RASSF2 A mRNA was the largest,which was 0.887.Conclusions HPV E2/E6,CDCP1,RASSF2 A methylation levels are closely related to the grade of cervical lesions and local immunity.The combined application has high clinical application value for clinical prediction of persistent HR-HPV infection,assessment of cervical lesions,and prevention of cervical cancer.