hTERC基因联合HPVL1壳蛋白检测对新疆维、汉妇女宫颈病变诊断价值的研究
发布时间：2018-06-09 04:14
本文选题：宫颈病变 + HPVL1壳蛋白 ； 参考：《新疆医科大学》2015年博士论文
【摘要】：目的:研究HPV L1壳蛋白和h TERC基因在新疆维吾尔族和汉族妇女宫颈脱落细胞中的表达情况及差异性,探讨维吾尔族与汉族宫颈癌发病机制的特点及差异性,评价HPV L1壳蛋白、hTERC基因及HPV L1壳蛋白和hTERC基因联合分析对新疆维吾尔族和汉族妇女宫颈病变的诊断价值。方法:收集2012年9月至2014年3月在新疆维吾尔自治区人民医院妇科门诊就诊或行宫颈癌机会性筛查的新疆维吾尔族和汉族妇女病例1160例,所有病例均进行TCT和HPV分型检测,选择其中HPV感染阳性或TCT阳性或两项同时阳性的病例纳入研究队列。所有纳入研究队列的病例均行阴道镜下活检送病理组织学检查,并通过免疫细胞化学法检测宫颈脱落细胞中HPV L1蛋白的表达情况,通过F1SH技术检测宫颈脱落细胞中h TERC基因的表达情况。结果:1、新疆维吾尔族与汉族妇女TCT结果的异常率无显著差异,且其ASCUS、LSIL、HSIL和SCC患者的构成比亦无显著差异;维吾尔族与汉族妇女HPV的阳性率没有显著差异,且其高危型HPV感染、混合型HPV感染和低危型HPV感染的构成比亦无显著差异。2、新疆维吾尔族与汉族妇女h TERC基因扩增的总阳性率无显著差异;维吾尔族与汉族妇女NILM组、ASCUS组、LSIL组、HSIL组和SCC组hTERC基因扩增的阳性率均没有显著差异;维吾尔族与汉族妇女正常或慢性炎症组、CIN1组、CIN2组、CIN3组和SCC组hTERC基因扩增的阳性率亦均无显著差异;hTERC基因的表达率不存在民族差异。维吾尔族与汉族妇女正常或慢性炎症组/CIN1组和CIN2~+组基因拷贝数的分布均无显著差异,且其正常或慢性炎症组/CIN1组和CIN2~+组TERC:CEP比例分布亦均无显著差异,hTERC基因的扩增类型不存在民族差异。3、对细胞学分组而言,维吾尔族和汉族妇女h TERC基因扩增阳性率的大小顺序均为:SCC组≈HSIL组㧐LSIL组㧐ASCUS组≈NILM组,随着细胞学分级的升高,各组中hTERC基因的扩增阳性率有增加的趋势;对组织学分组而言,其大小顺序均为:SCC组≈CIN 3组㧐CIN 2组㧐CIN 1组≈正常或慢性炎症组,随着宫颈病变恶性程度的增加,各组中hTERC基因的扩增阳性率有增加的趋势,hTERC基因的表达与宫颈病变的恶性程度呈正相关。4、新疆维吾尔族与汉族妇女hpvl1壳蛋白的总阳性表达率无显著差异,其正常或慢性炎症组、cin1组、cin2组、cin3组和scc组hpvl1壳蛋白表达的阳性率均无显著差异;其nilm组、ascus组、lsil组、hsil组和scc组hpvl1壳蛋白表达的阳性率亦均无显著差异。hpvll壳蛋白的表达率不存在民族差异。5、对于新疆维吾尔族妇女和汉族妇女而言,hpvl1壳蛋白表达的阳性率在c1n1组为最高,高于正常或慢性炎症组及其它高病变组;对于不同宫颈病变组而言,hpvl1壳蛋白表达的阳性率随宫颈病变恶性程度的增加而降低,呈负相关;对于不同细胞学分级而言,hpvl1壳蛋白表达的阳性率在lsil组为最高,高于nilm组和ascus组及其他更高级别的细胞学分组。而且,自lsil组起,随着细胞学分级的升高,hpvl1壳蛋白表达的阳性率呈下降的趋势,呈负相关。新疆维吾尔族和汉族妇女宫颈脱落细胞中hpvll壳蛋白的表达与宫颈病变的恶性程度均呈负相关,其可能是宫颈低度鳞状上皮内病变预后的保护性因素之一。6、对于hpv感染阳性的新疆维吾尔族妇女与汉族妇女而言,其宫颈脱落细胞中hpvl1壳蛋白表达的总阳性率无显著差异,且其高危型感染者、混合型感染者和低危型感染者中hpvl1壳蛋白表达的阳性率亦均无显著差异。维吾尔族和汉族妇女低危型感染者与混合型感染者hpvl1壳蛋白表达的阳性率均无显著差异,高危型感染者hpvl1壳蛋白表达的阳性率低于低危型感染者和混合型感染者。7、hpvl1壳蛋白诊断新疆维吾尔族和汉族妇女宫颈高度病变cin2~+时,其适用人群为具有宫颈鳞状上皮内病变的患者,其灵敏度、正确率和阳性预测价值较高,特异度和阴性预测价值较低,且不存在民族差异。其诊断价值中等(roc曲线下面积:维吾尔族为0.699,汉族为0.705)。8、hterc基因检测诊断宫颈高度病变cin2~+时,其适用人群为正常或慢性炎症患者及具有宫颈鳞状上皮内病变的患者,其灵敏度、特异度、正确率、阳性预测价值和阴性预测价值均较高,且不存在民族差异。其诊断价值较高(roc曲线下面积:维吾尔族为0.875,汉族为0.871)。9、hpvl1壳蛋白联合hterc基因检测诊断宫颈高度病变cin2~+时,其适用人群为具有宫颈鳞状上皮内病变的患者,其灵敏度、正确率和阳性预测价值较高,特异度和阴性预测价值较低,且不存在民族差异。其诊断价值中等(roc曲线下面积:维吾尔族为0.706,汉族为0.699)。10、当应用对象为具有宫颈鳞状上皮内病变的患者时,hpvl1壳蛋白、hterc基因和hpvl1壳蛋白联合hterc基因诊断新疆维吾尔族妇女与汉族妇女宫颈高度病变cin2~+的效率为:hterc基因㧐hpvl1壳蛋白联合hterc基因≈hpvl1壳蛋白。11、hpvl1/hterc表达的状态随着宫颈病变程度的升高可排列为hpvl1(-)/hterc(-)、l1(+)/hterc(-)、hpvl1(+)/hterc(+)和hpvl1(-)/hterc(+)。结论:1、新疆维吾尔族与汉族妇女宫颈脱落细胞中hterc基因的表达和hpvl1壳蛋白的表达没有民族差异。2、新疆维吾尔族和汉族妇女宫颈脱落细胞中hterc基因的表达与宫颈病变的恶性程度均呈正相关,HPV Ll壳蛋白的表达与宫颈病变的恶性程度均呈负相关。3、HPV L1壳蛋白诊断新疆维吾尔族和汉族妇女宫颈高度病变CIN2~+时,其适用人群为具有宫颈鳞状上皮内病变的患者,其灵敏度、正确率和阳性预测价值较高,特异度和阴性预测价值较低,各项指标之间均不存在民族差异,诊断价值中等;hTERC基因检测诊断宫颈高度病变CIN2~+时,其适用人群为正常或慢性炎症患者及具有宫颈鳞状上皮内病变的患者。其灵敏度、特异度、正确率、阳性预测价值和阴性预测价值均较高,各项指标之间均不存在民族差异,诊断价值较高;HPV L1壳蛋白联合hTERC基因检测筛查/诊断宫颈高度病变CIN2~+时,其适用人群为具有宫颈鳞状上皮内病变的患者,其灵敏度、正确率和阳性预测价值较高,特异度和阴性预测价值较低,各项指标之间均不存在民族差异,诊断价值中等。4、当应用对象为具有宫颈鳞状上皮内病变的患者时,h TERC基因诊断维吾尔族妇女和汉族妇女宫颈高度病变CIN2~+的效率高于HPV L1壳蛋白及HPV L1壳蛋白和hTERC基因联合分析。5、HPV L1/hTERC的表达状态随宫颈病变严重程度的不同而变化,其表达时序可能反映了宫颈病变的发展过程。
[Abstract]:Objective: To study the expression of HPV L1 shell protein and H TERC gene in the cervical exfoliated cells of Uygur and Han women in Xinjiang and to explore the characteristics and differences of the pathogenesis of cervical cancer in Uygur and Han nationality, and to evaluate the combined analysis of HPV L1 shell protein, hTERC gene and HPV L1 shell egg white and hTERC gene for the Uygur nationality in Xinjiang and the Uygur and hTERC genes. Diagnostic value of cervical lesions of Han women. Methods: 1160 cases of Uygur and Han women in Xinjiang from September 2012 to March 2014 at the the Xinjiang Uygur Autonomous Region people's Hospital Department of gynaecologic outpatient or cervical cancer screening were screened in Xinjiang Uygur and Han women. All cases were detected by TCT and HPV typing, of which HPV infection was positive or TCT positive All the two positive cases were included in the study cohort. All the cases included in the cohort were examined by biopsy under colposcopy, and the expression of HPV L1 protein in the exfoliated cells of the cervix was detected by immunocytochemistry and the expression of H TERC gene in the exfoliated cells of the cervix was detected by F1SH. Results: 1. There was no significant difference in the abnormal rate of TCT between the Uygur and Han women, and there was no significant difference in the constituent ratio of ASCUS, LSIL, HSIL and SCC, and there was no significant difference in the positive rate of HPV between Uygur and Han women, and there was no significant difference in the proportion of the high-risk HPV infection, the mixed HPV infection and the low risk HPV infection,.2, the Xinjiang dimension. There was no significant difference in the total positive rate of H TERC gene amplification between the Han and Han women. There was no significant difference in the positive rate of hTERC gene amplification between the Uygur and Han women NILM group, ASCUS group, LSIL group, HSIL group and SCC group, and the positive and chronic inflammation group of Uygur and Han women, CIN1 group, CIN2 group, CIN3 group and SCC group amplification gene amplification. There was no significant difference in sex ratio. There was no national difference in the expression rate of hTERC gene. There was no significant difference in the distribution of gene copies between /CIN1 and CIN2~+ groups in normal or chronic inflammatory groups of Uygur and Han women, and there was no significant difference in the proportion of TERC:CEP in the normal or chronic inflammation group between the /CIN1 group and the CIN2~+ group, and the amplification of the hTERC gene. There was no national difference.3. For the cytological group, the positive rates of H TERC gene amplification in Uygur and Han women were all: SCC group HSIL group? LSIL group? ASCUS group NILM group. With the increase of cytological classification, the positive rate of hTERC gene amplification in each group was increasing; for histological grouping, the size of the group was the size of the group. The sequence is: group SCC CIN 3? CIN 2 groups? CIN 1 groups of normal or chronic inflammation group, with the increase of the malignant degree of cervical lesions, the positive rate of hTERC gene amplification in each group is increasing, the expression of hTERC gene is positively related to the malignant degree of cervical lesions, and the total positive of hpvl1 shell protein in Uygur and Han women in Xinjiang There was no significant difference in the expression rate. There was no significant difference in the positive rate of the expression of hpvl1 shell protein in the normal or chronic inflammation group, cin1 group, Cin2 group, CIN3 group and SCC group, and there was no significant difference in the positive rate of hpvl1 shell protein expression in group nilm, ASCUS, LSIL, HSIL and SCC groups. In our women and Han women, the positive rate of hpvl1 protein expression was highest in the c1n1 group, higher than in the normal or chronic inflammation group and in other high pathological groups. The positive rate of hpvl1 shell protein expression decreased with the increase of the malignant degree of cervical lesions and was negatively correlated with different cervical lesions. The positive rate of hpvl1 protein expression was highest in group LSIL, higher than that in group nilm and ascus and other higher grade cytology groups. Moreover, the positive rate of hpvl1 shell protein expression decreased with the increase of cytological classification in group LSIL, and negative correlation was found. Hpvll shell eggs in cervical exfoliative cells of Xinjiang vim and Han women There is a negative correlation between the expression of white and the malignancy of cervical lesions, which may be one of the protective factors for the prognosis of the cervical low-grade intraepithelial lesions,.6. For the Xinjiang Uygur women with positive HPV infection, the total positive rate of the hpvl1 shell protein in the cervical exfoliative cells of the cervix is not significantly different, and the high risk type is also found in the cervical exfoliative cells. There was no significant difference in the positive rate of hpvl1 protein expression in the infected, mixed and low risk infected people. There was no significant difference in the positive rate of hpvl1 shell protein expression between the Uygur and Han women with low risk infection and mixed infection. The positive rate of hpvl1 shell egg white expression in high risk infected people was lower than that of those with low risk. .7, hpvl1 shell protein in the diagnosis of cervical high lesion cin2~+ in Uygur and Han women in Xinjiang. The sensitivity, accuracy and positive predictive value of the patients with cervical squamous intraepithelial lesion were higher, the specificity and negative predictive value were lower, and there was no national difference. The diagnostic value was moderate (RO The area under the C curve: the Uygur nationality is 0.699, the Han is 0.705).8. When the hTERC gene is used to detect the high lesion of the cervix, the application population is the normal or chronic inflammation patients and the patients with cervix squamous intraepithelial lesion, whose sensitivity, specificity, correct rate, positive predictive value and negative predictive value are high, and there are no ethnic groups. The diagnostic value is high (the area under the ROC curve: the Uygur is 0.875, the Han is 0.871).9, and the hpvl1 shell protein combined with the hTERC gene for the diagnosis of cervical high lesion cin2~+, the suitable population is the patient with the cervical squamous intraepithelial lesion, whose sensitivity, accuracy and positive predictive value are higher, the specificity and negative predictive value are higher. The diagnostic value is moderate (the area under ROC curve: Uygur is 0.706, Han is 0.699).10. When applied to patients with cervical squamous intraepithelial lesion, hpvl1 shell protein, hTERC gene and hpvl1 shell protein are combined with hTERC gene to diagnose the cervical high disease of Xinjiang Uygur women and Han women The efficiency of changing cin2~+ is: the hTERC gene? Hpvl1 shell protein combined with the hTERC gene hpvl1 shell protein.11. The state of hpvl1/hterc expression can be arranged as hpvl1 (-) /hterc (-), L1 (+) /hterc (+), hpvl1 (+) and (+)). Conclusion: 1, the cervical exfoliative cells of the Uygur and Han women in Xinjiang There was no national difference between the expression of the protein and the expression of hpvl1 shell protein. The expression of hTERC gene in the cervical exfoliated cells of the Uygur and Han women in Xinjiang was positively correlated with the malignant degree of cervical lesions. The expression of HPV Ll shell protein was negatively correlated with the malignant degree of cervical lesions, and the HPV L1 shell protein was used to diagnose the Uygur and Han nationality in Xinjiang. The sensitivity, accuracy and positive predictive value of the patients with cervical squamous intraepithelial lesion CIN2~+ are high, the specificity and negative predictive value are low, and there is no national difference between the indexes and the diagnostic value is moderate among all the indexes. When the hTERC gene is detected for the diagnosis of the high lesion of the cervix, CIN2~+, The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of the patients with normal or chronic inflammation and squamous intraepithelial lesion of the cervix were higher. There was no national difference between all the indexes and the value of diagnosis was higher. HPV L1 shell protein combined with hTERC gene to detect and diagnose the high disease of the cervix. When the CIN2~+ was changed, the patients with cervical squamous intraepithelial lesion were of high sensitivity, accuracy and positive predictive value, and the specificity and negative predictive value were low. There was no national difference between the indexes, and the diagnostic value was medium.4. When the application object was the patients with cervical squamous intraepithelial lesion, the H TERC base was found. The diagnostic efficiency of CIN2~+ in Uygur women and Han women is higher than that of HPV L1 shell protein and HPV L1 shell protein and hTERC gene to analyze.5. The expression of HPV L1/hTERC varies with the severity of cervical lesions. The expression timing may reflect the development of cervical lesions.
【学位授予单位】：新疆医科大学
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R737.33
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本文编号：1998846
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