宫颈癌及癌前病变预警因子的研究

发布时间：2018-03-23 22:36

本文选题：人乳头状瘤病毒　切入点：宫颈癌　出处：《新疆医科大学》2015年博士论文

【摘要】：目的:在维族、汉族HPV筛检出阳性的女性人群中分别检测血清中IL-2及IL-6、IL-10、IFN-γ、人乳头状瘤病毒(HPV)L1抗体,同时检测HPVLI壳蛋白在组织中和TCT保存液中的表达;组织中HPV16DNA L1、E6、E7基因的载量,HPV16L1、HPVE6、E7蛋白、HPV E6/E7mRNA在宫颈病变组织中的表达情况,评价这些检测在宫颈病变筛查及宫颈癌风险预警中的作用,能为用于临床提供一些理论依据,探索维族妇女有别于汉族妇女宫颈病变的发病原因及临床相关指标。方法:收集2013年8月~2015年6月新疆自治区人民医院妇科和门诊都自己愿意接受宫颈癌机会性筛查维吾尔族妇女,分别利用HC-2、HPV DNA、HPV分型技术确定HPV的型别及感染情况,分为宫颈炎组、CINI组、CINII-III组、宫颈癌组,利用酶联免疫吸附法(ELISA)、免疫组化法分别测定患者血清、宫颈组织中IL-2及IL-6、IL-10、IFN-γ的水平;对HPV结果阳性的其中197例标本分别用免疫细胞化学法、免疫组化法检测HPV L1壳蛋白在宫颈脱落细胞中、宫颈组织中的表达,利用RT-PCR技术检测HPV16DNA L1、E6、E7基因、western-blot技术检测HPV16L1、E6、E7蛋白水平,同时利用酶联免疫吸附法(ELISA)测定该197份标本的患者血清中HPV16L1抗体的表达;对宫颈病变患者采用APTIMA方法进行高危型HPV E6/E7 mRNA检测,以宫颈组织病理学结果为标准。结果:IFN-γ在宫颈组织中的表达均随宫颈病变级别的增加而减少,IL-10的表达均随着宫颈病变级别的加重而增加,差异均有统计学意义(P0.05)。各个宫颈病变级别的患者血清中IL-2、IFN-γ的水平均随着宫颈病变严重程度的增加而减少,IL-6、IL-10的水平均随着宫颈病变级别的加重而增加,差异均有统计学意义(P0.05)。分层后维吾尔族妇女与汉族妇女之间,IL-6、IL-10的水平比较无统计学差异(均P0.05)。HPV L1壳蛋白在组织中和脱落细胞液中阳性表达率随着宫颈病变级别的增加呈下降的趋势,差异均有统计学意义(P0.05)。血清中HPV16L1抗体随着宫颈病变级别的加重,抗体水平升高,差异有统计学意义(P0.05)。维吾尔族妇女与汉族妇女之间比较无统计学差异(均P0.05)。宫颈组织中随着宫颈病变级别的加重HPV16E6、E7蛋白表达增加,差异有统计学意义(P0.05);宫颈组织中HPVE6/E7mRNA随着宫颈病变严重程度的增加而增加,差异有统计学意义(P0.05),而且HPVE7、E6蛋白和HPVE6/E7mRNA表达具有相关性,差异有统计学意义。在两个民族之间不同病理级别中进行比较,HPVE6/E7mRNA差异无统计学意义。HPV E6/E7 mRNA检测能预测高级别宫颈病变,阴性预测值=81.01%;阳性预测值=72.88%;准确性=76.14%。病理类型分层汉族和维吾尔族HPV16E7DNA载量的差别均无统计学意义。结论:宫颈病变和子宫颈癌的最主要致病因素是HPV持续感染;各组患者血清中IL-2、IFN-γ的水平均随着宫颈病变严重程度的增加而减少,IL-6、IL-10的水平均随着宫颈病变级别的加重而增加,IFN-γ在宫颈组织中的表达随着宫颈病变严重程度的增加而减少,IL-10的表达均随着宫颈病变级别的加重而增加;HPV L1壳蛋白的阳性表达随着宫颈病变的级别增加而下降,维族汉族之间相等级别宫颈病变之间的表达无差异;HPV16E6、E7蛋白、HPVE6/E7 mRNA在组织中的表达随着宫颈病变级别的加重表达增加,HPVL1蛋白检测及HPVE6/E7 mRNA有望成为预测维吾尔族宫颈病变严重程度的重要生物学标志物。
[Abstract]:Objective: in the Uygur, Han HPV screening were detected positive women in IL-2 and IL-6, IL-10 in serum, IFN- gamma, human papilloma virus (HPV) L1 antibody, simultaneous detection of HPVLI protein in the tissue and shell TCT to save the expression in the liquid; HPV16DNA in L1, E6, load, E7 gene HPV16L1, HPVE6, E7 protein, expression of HPV E6/E7mRNA in cervical lesions, evaluate the effects of these test in screening of cervical lesions and cervical cancer risk prediction, can provide some theoretical basis for exploration for clinical, Uighur women is different from the Han nationality women in etiology of cervical lesions and clinical indicators. Methods: from August 2013 June ~2015 in Xinjiang Autonomous Region People's hospital gynecological outpatient and are themselves willing to accept the opportunistic screening for cervical cancer in Uygur women, respectively by HC-2, HPV DNA, HPV genotyping technology to determine the type and infection of HPV, Divided into CINI group, cervicitis group, CINII-III group and cervical cancer group, using enzyme-linked immunosorbent assay (ELISA), the serum was measured by immunohistochemistry method respectively, IL-10 IL-2 and IL-6 in cervical tissue, IFN- gamma level; immunocytochemistry were used to HPV positive results from 197 cases. Immunohistochemical detection of HPV L1 capsid protein in cervical exfoliated cells, expression in cervical tissue, detected by HPV16DNA L1, RT-PCR E6, E7 gene, HPV16L1 detection, Western-blot E6, E7 protein level by enzyme-linked immunosorbent assay (ELISA) expression of HPV16L1 antibody of the 197 specimens of serum determination of the detection of high-risk HPV E6/E7; mRNA APTIMA method on patients with cervical lesions in the cervical tissue, the pathological results. Results: IFN- expression in cervical tissues were increased with the level of cervical lesions and decrease the expression of IL-10 was Increases with the level of cervical lesions increased, the differences were statistically significant (P0.05). The IL-2 level in serum of patients with cervical lesions, IFN- gamma levels were decreased with the increase of the severity of cervical lesions and IL-6, IL-10 levels were increased with the increased level of cervical lesions, the differences were statistically significant (P0.05). IL-6, after stratification in Uigur and Han women, no significant differences between the levels of IL-10 (P0.05).HPV L1 protein positive cells in the liquid shedding rate decreased with the level of cervical lesions in the tissue and, the differences were statistically significant (P0.05). The serum HPV16L1 antibody with aggravation of cervical lesions the level of antibody level increased, the difference was statistically significant (P0.05). Between Uigur and Han women had no significant difference (P0.05) in cervical tissue with. HPV16E6 increased the level of cervical lesions, the expression of E7 protein increased, the difference was statistically significant (P0.05); HPVE6/E7mRNA in cervical tissue increased with the severity of cervical lesions, the difference was statistically significant (P0.05), and HPVE7, E6 protein and HPVE6/E7mRNA expression has correlation, the difference was statistically significant. Compared in different pathological the level of HPVE6/E7mRNA between the two groups, there was no significant difference in.HPV E6/E7 mRNA can predict the detection of high grade cervical lesions, negative predictive value, positive predictive value of =81.01%; =72.88% = 76.14%.; the accuracy of pathological types of layered Han and Uygur HPV16E7DNA load difference was not statistically significant. Conclusion: the main pathogenesis of cervical lesions and cervical cancer is HPV persistent infection; serum IL-2 groups, IFN- gamma levels were reduced with the increase of the severity of cervical lesions and IL-6, IL-1 0 levels were increased with the aggravation of cervical lesions and IFN- expression in cervical tissues decreased with the severity of cervical lesions, the expression of IL-10 was increased with increasing the level of cervical lesions; the positive expression of HPV L1 capsid protein decreased with the level of cervical lesions increased, no difference between the expression of between Uygur and Han people in equal levels of cervical lesions; HPV16E6, E7 protein, the expression of HPVE6/E7 mRNA in tissues with the level of cervical lesions increased increased expression of HPVL1 protein detection and HPVE6/E7 mRNA is expected to become an important biological prediction of Uygur cervical lesion severity markers.

【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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