血清DNA甲基转移酶1、DNA甲基转移酶3a在宫颈癌及癌前病变中的表达及与人乳头瘤病毒感染的相关性

Expressions of serum DNMT1 and DNMT3a in patients with cervical cancer and precancerous lesions and their correlation with HPV infection

目的检测宫颈癌及癌前病变病人血清中DNA甲基转移酶1(DNMT1)、DNA甲基转移酶3a(DNMT3a)表达水平,探讨二者与人乳头瘤病毒(HPV)感染的相关性。方法选取2017年9月至2019年9月于焦煤集团中央医院收治住院的宫颈癌病人58例及癌前病变病人70例作为观察组。选取同期入院体检的正常女性志愿者50例作为对照组。采用酶联免疫吸附(ELI⁃SA)法检测血清中DNMT1、DNMT3a表达水平,检测各组HPV感染情况,将观察组根据是否感染HPV分为HPV感染组和HPV未感染组,比较两组间血清DNMT1、DNMT3a表达水平。分析血清DNMT1、DNMT3a水平与宫颈癌及癌前病变组病人病情严重程度及HPV感染类型的关系。结果宫颈癌及癌前病变病人血清DNMT1[(44.72±9.36)μg/L、(26.78±5.84)μg/L比(13.03±2.65)μg/L]、DNMT3a[(607.48±125.19)μg/L、(415.03±82.56)μg/L比(346.12±67.34)μg/L]表达显著高于对照组(P<0.05),宫颈癌病人血清DNMT1、DNMT3a表达显著高于癌前病变组(P<0.05)。血清DNMT1、DNMT3a水平与宫颈癌病人FIGO分期、CIN分级、HPV危险程度均相关(P<0.05)。血清DNMT1、DNMT3a诊断宫颈癌的AUC分别为0.918、0.875,截断值分别为36.049μg/L、563.431μg/L,特异性分别为92.9%、94.3%,敏感度分别为82.8%、70.7%;二者联合诊断宫颈癌的AUC为0.960,特异性为94.3%,敏感度为91.4%。各组HPV感染情况结果显示,宫颈癌组病人HPV阳性率最高为100.00%,宫颈癌前病变组HPV阳性率为61.43%,对照组HPV阳性率为6.00%,三组HPV感染情况差异有统计学意义(P<0.05)。HPV感染组病人及健康女性血清DNMT1、DNMT3a表达水平高于HPV未感染组,差异有统计学意义(P<0.05)。结论宫颈癌及癌前病变病人血清DNMT1、DN⁃MT3a呈高表达,宫颈癌病人HPV感染率显著高于癌前病变病人,HPV感染病人血清DNMT1、DNMT3a表达水平升高,且高表达DNMT1、DNMT3a水平与宫颈癌及癌前病变病人病情严重、HPV感染高危相关。

Objective To detect the expression levels of DNA methyltransferase 1(DNMT1)and DNA methyltransferase 3a(DN⁃MT3a)in serum of patients with cervical cancer and precancerous lesions,and to explore the correlation between them and HPV infec⁃tion.Methods A total of 58 patients with cervical cancer and 70 patients with precancerous lesions in Central Hospital of Coking Coal Group from September 2017 to September 2019 were selected as the observation group.And another 50 normal female volunteers who had physical examination in the same period were selected as the control group.The expression levels of DNMT1 and DNMT3a in se⁃rum were detected by enzyme-linked immunosorbent assay(ELISA),and HPV infection in each group was detected,the observation group was assigned into HPV infected group and HPV uninfected group according to whether HPV was infected,and the expression lev⁃els of DNMT1 and DNMT3a in serum between the two groups were compared.The relationship between serum DNMT1,DNMT3a levels and the severity of cervical cancer and precancerous lesions,and the type of HPV infection were analyzed.Results The expressions of serum DNMT1 and DNMT3a in patients with cervical cancer and precancerous lesions were significantly higher than those in the con⁃trol group[DNMT1(44.72±9.36)μg/L,(26.78±5.84)μg/L vs.(13.03±2.65)μg/L,DNMT3a:(607.48±125.19)μg/L,(415.03±82.56)μg/L vs.(346.12±67.34)μg/L,P<0.05],and the expressions of serum DNMT1 and DNMT3a in patients with cervical cancer were signifi⁃cantly higher than those in patients with precancerous lesions(P<0.05).The levels of serum DNMT1 and DNMT3a were correlated with FIGO stage,CIN grade and risk of HPV(P<0.05).The AUC of serum DNMT1 and DNMT3a for the diagnosis of cervical cancer were 0.918 and 0.875,respectively,the cut-off values were 36.049μg/L and 563.431μg/L,the specificities were 92.9%and 94.3%,and the sensitivity was 82.8%and 70.7%;the AUC of the combined diagnosis of cervical cancer was 0.960,the specificity was 94.3%,and the sensitivity was 91.4%.The results of HPV infection in each group showed that the HPV positive rate was 100.00%in the cervical can⁃cer group,which was the highest,at the same time,that was 61.43%in the cervical precancerous lesion group and 6.00%in the control group,and the difference in HPV infection among the three groups was statistically significant(P<0.05).The expression levels of serum DNMT1 and DNMT3a in the HPV infection group and healthy women were higher than those in the HPV uninfected group,and the dif⁃ference was statistically significant(P<0.05).Conclusion The expressions of DNMT1 and DNMT3a are high in cervical cancer and precancerous lesions,the HPV infection rate of patients with cervical cancer is significantly higher than that of patients with precancer⁃ous lesions,the expression levels of serum DNMT1 and DNMT3a are increased in patients with HPV infection,and the high expression levels of DNMT1 and DNMT3a are associated with the severity of cervical cancer and precancerous lesions and the high risk of HPV in⁃fection.