首页|透明质酸合成酶1和ATP酶磷脂转运10a基因甲基化定量检测在宫颈癌早期诊断中的应用价值

透明质酸合成酶1和ATP酶磷脂转运10a基因甲基化定量检测在宫颈癌早期诊断中的应用价值

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目的 探讨透明质酸合成酶1(HAS1)、ATP酶磷脂转运10a(ATP10a)基因甲基化定量检测在宫颈癌早期诊断中的应用价值。方法 选取2022年2-9月于秦皇岛市第一医院就诊,存在细胞学异常和/或高危型人乳头瘤病毒(HR-HPV)感染,且具有明确组织学病理结果的145例患者,采用实时荧光定量甲基化特异性PCR(QMSP)检测HAS1、ATP10a基因在不同程度宫颈病变患者宫颈脱落细胞中的甲基化水平。以活检病理检查结果为金标准,确定HAS1、ATP10a基因甲基化诊断宫颈高级别鳞状上皮内病变(HSIL)+宫颈鳞癌(SCC)的临界值,并依据临界值将定量资料转换为定性资料,采用灵敏度、特异度、阳性预测值、阴性预测值及受试者工作特征(ROC)曲线下面积(AUC)等指标评估各种筛查方法诊断HSIL+(包括HS1L+SCC)的效能。结果 纳入了 77例宫颈低级别鳞状上皮内病变(LS1L)-患者(病理检查结果为正常/宫颈炎,LSIL),68例HSIL+患者(病理检查结果为HSIL,SCC)。在LSIL-组,HAS1、ATP10a基因甲基化水平分别为0。067(0。015,1。920),0。024(0。008,0。129),均低于 HSIL+组的 1。509(0。062,1 080。749),1。042(0。011,526。086),组间比较差异均有统计学意义(均P<0。05)。选取0。185、0。197分别作为HAS1、ATP10a基因甲基化阳性的临界值,在LS1L-组中,液基薄层细胞学检查(TCT)结果异常率,HR-HPV检测阳性率,HAS1+ATP10a基因甲基化阳性率,HR-HPV检测联合HAS1+ATP10a基因甲基化阳性率分别为 50。65%、85。71%、38。96%、36。36%,均显著低于 HSIL+组(69。12%、95。59%、79。41%、75。00%)。HR-HPV 检测、TCT、HAS1+ATP10a基因甲基化、HR-HPV检测联合HAS1+ATP10a基因甲基化诊断HSIL+的灵敏度分别为95。59%、69。12%、79。41%、75。00%,特异度分别为 14。29%、49。35%、61。04%、63。64%,阳性预测值分别为 49。62%、54。65%、69。05%、64。56%,阴性预测值分别为 78。57%、64。41%、77。05%、74。24%,AUC 分别为 0。549、0。592、0。702、0。693。结论 宫颈脱落细胞中HAS1、ATP10a基因甲基化水平随宫颈病变严重程度加重而升高,HASJ、ATP10a基因甲基化检测HSIL+病变具有较高的临床价值,有望成为早期诊断宫颈癌的方法。
Application value of quantitative detection of hyaluronic acid synthase 1 and ATPase phospholipid transport 10a gene methylation in early diagnosis of cervical cancer
Objective To explore the application value of quantitative detection of hyaluronic acid synthase 1(HAS1)and ATPase phospholipid transport 10a(ATP10a)gene methylation in early diagnosis of cervical cancer.Methods A total of 145 patients with cytolog-ical abnormalities and/or high-risk human papillomavirus(HR-HPV)infection and histopathological results were selected from the First Hospital of Qinhuangdao from February to September 2022.Real-time fluorescence quantitative methylation specific PCR(QMSP)was used to detect the methylation levels of HAS1 and ATP10a gene in cervical exfoliated cells of patients with different degrees of cervical lesion.Tak-ing biopsy histopathological results as the gold standard,the cut-off values of HAS1 and ATP10a gene methylation in diagnosis of high-grade squamous intraepithelial lesion(HSIL)and squamous carcinoma of the cervix(SCC)were determined,and the quantitative data were conver-ted into qualitative data according to the cut-off values,and the clinical efficacy of various screening methods in diagnosis of HSIL+(HSIL+SCC)was evaluated according to sensitivity,specificity,positive predictive value,negative predictive value,and the area under receiver op-erator characteristic(ROC)curve(AUC).Results A total of 77 patients with LSIL-(normal/cervicitis,LSIL)and 68 HSIL+(HSIL,SCC)were included.In LSIL-group,the methylation levels of HAS1 and ATP10a gene were 0.067(0.015,1.920),0.024(0.008,0.129),respectively,which were lower than those in HSIL+group[1.509(0.062,1 080.749),1.042(0.011,526.086)],there were statistically significant differences(both P<0.05).0.185 and 0.197 were selected as the cut-off values for positive methylation of HAS1 and ATP10a gene,respectively.In LSIL-group,the abnormal rate of liquid-based thin-layer cytology(TCT)results,the positive rate of HR-HPV detection,the positive rate of HAS1+ATP10a gene methylation,and the positive rate of HR-HPV detection combined with HAS1+ATP10a gene methylation were 50.65%,85.71%,38.96%,and 36.36%,respectively,which were lower than those in HSIL+group(69.12%,95.59%,79.41%,and 75.00%,respectively).In the diagnosis of HSIL+,the sensitivities of HR-HPV detection,TCT,HAS1+ATP10a gene methylation,HR-HPV detection combined with HAS1+ATP10a gene methylation were 95.59%,69.12%,79.41%,and 75.00%,respectively,the specificities were 14.29%,49.35%,61.04%,and 63.64%,respectively,the positive predictive values were 49.62%,54.65%,69.05%,and 64.56%,respectively,the neg-ative predictive values were 78.57%,64.41%,77.05%,and 74.24%,respectively,AUC values were 0.549,0.592,0.702,and 0.693,respectively.Conclusion The methylation levels of HASI and ATP10a gene in cervical exfoliated cells increase with the severity of cervical lesion.HAS1 and ATP10a gene methylation have high clinical value in detection of HSIL+lesions,which is expected to be a means for early diagnosis of cervical cancer.

Hyaluronic acid synthase 1 geneATPase phospholipid transport 10a geneMethylationCervical squamous intraepithelial lesionCervical cancer

陈思思、唐伊蔓、姜晓丹、王慧芳、金海红

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秦皇岛市第一医院,河北秦皇岛 066000

河北北方学院

秦皇岛市第二医院

透明质酸合成酶1基因 ATP酶磷脂转运10a基因 甲基化 宫颈鳞状上皮内病变 宫颈癌

2025

中国妇幼保健
中华预防医学会 吉林省医学期刊社

中国妇幼保健

影响因子:1.486
ISSN:1001-4411
年,卷(期):2025.40(2)