人类白细胞抗原-E在浆液性卵巢癌患者中的表达及临床应用研究

发布时间：2018-01-02 01:01

本文关键词：人类白细胞抗原-E在浆液性卵巢癌患者中的表达及临床应用研究　出处：《山东大学》2016年硕士论文　论文类型：学位论文

更多相关文章： HLA-E sHLA-E 浆液性卵巢癌 CA125

【摘要】：背景：卵巢的恶性肿瘤是女性生殖系统最常见的恶性肿瘤之一,在每个年龄段中均有发病,而上皮性肿瘤好发于50岁以后的妇女,5年生存率一直处于30%到40%之间,死亡率均高于其他妇科恶性肿瘤,位于第一位,已经成了对女性身体健康和生存影响最大的肿瘤之一。在上皮性卵巢癌中浆液性卵巢癌(SOC)占75%,其5年的生存率却很低仅为30.6%。目前仍缺乏简便实用而敏感性特异性高的诊断方法,大部分患者就诊时已错过手术的最佳时期发展到临床晚期。所以及早筛查、及早发现、及早诊断、及早治疗是卵巢癌患者维持生命质量和提高生存概率的关键。人类白细胞抗原-E (HLA-E)是一种非经典的HLA I类分子,很多研究表明其参与肿瘤的免疫逃逸,并且很多文献报道其在多种肿瘤组织和肿瘤患者血液中出现高表达。关于HLA-E在浆液性卵巢中表达的文献少见。所以我们应用免疫组化和酶联免疫吸附试验(ELISA)的方法研究HLA-E在SOC中的表达,以探讨其在SOC发病机制中的作用及作为SOC诊断和预后指标的可能性。目的：检测SOC患者癌组织中HLA-E的表达和患者血清中sHLA-E的表达。比较HLA-E的表达与肿瘤临床各相关参数间的关系,从而研究HLA-E在SOC的发生与发展中的机制,同已广泛应用的CA125进行比较,评价sHLA-E在SOC临床诊断中的应用价值。方法：切片组织为山东大学附属省立医院病理科2012.07-2015.09保存完好的SOC标本共48例,年龄为26-72岁。根据FIGO2014卵巢癌分期标准,分成早期(Ⅰ-Ⅱ)和晚期(Ⅲ-Ⅳ),其中早期和晚期分别为18和30例。然后再选取12例卵巢良性肿瘤做为对照。血标本为2015年7月到2015年11月在山东大学附属省立医院妇科住院治疗的浆液性卵巢癌、卵巢囊肿和子宫肌瘤患者共42例,其中SOC患者和良性肿瘤患者组分别为30例和12例。1、SOC患者组织中HLA-E的表达采用免疫组化的方法来检测48例SOC和12例卵巢良性肿瘤组织中HLA-E的表达情况,并评价SOC患者中HLA-E的表达情况与其临床相关参数之间的关系。2, sHLA-E在SOC患者血清中的表达应用ELISA法检测30例SOC患者和12例良性肿瘤患者(对照组)血清中sHLA-E的浓度,对比两组研究对象血清中sHLA-E浓度的不同,并比较其与SOC患者的临床相关参数之间的相关性。3、评价sHLA-E在SOC诊断中的应用价值通过ROC曲线分别比较sHLA-E、CA125对SOC的诊断价值,然后将两个指标的检测结果进行比较,评价sHLA-E在SOC诊断中的应用价值。结果：1、免疫组织化学染色后在细胞的胞膜和(或)胞浆上出现黄-棕色颗粒显示结果阳性,根据染色深浅强度和细胞占整体的比例进行综合评分。结果显示HLA-E在SOC肿瘤组织中阳性率为72.92%(35/48)明显高于卵巢良性组织中的阳性率8.3%(1/12),差异有统计学意义(P0.05)。HLA-E表达的阳性率与SOC的临床分期密切相关。但与患者年龄和肿瘤分化程度无关。2、sHLA-E在SOC患者血清中浓度均值和标准差为767.03±202.19ng/mL而对照组患者则为616.06±86.39ng/mL, SOC患者血清中sHLA-E浓度明显高于对照组(P0.05)。3、分析ROC曲线知sHLA-E在SOC的诊断中具有一定的价值。sHLA-E的截点值为631.90 ng/mL,其诊断的特异性和敏感性分别为：78.6%和75%。结论：1、HLA-E在SOC肿瘤组织和患者血清中的表达明显高于对照组,说明其在SOC的发生、发展中有重要的作用。2、sHLA-E在SOC诊断中的敏感性高于CA125,但特异性却低于CA125,具有一定潜在的临床应用价值,有成为SOC诊断指标的可能性。
[Abstract]:Background: ovarian cancer is one of the most common malignant tumor of the female reproductive system, there were cases in each age group, and epithelial tumor in women after the age of 50, 5 year survival rate has been at 30% to 40%, the mortality rate was higher than that of other gynecologic malignant tumors located in the first place, has become a one of the biggest tumor of the female body health and survival. In epithelial ovarian cancer in serous ovarian cancer (SOC) accounts for 75% of its 5 year survival rate is very low only 30.6%. there is still a lack of diagnosis method is simple and practical and high sensitivity and specificity, the best period of most patients have missed surgery the development of clinical stage. So the early screening, early detection, early diagnosis, early treatment is the quality of life of patients with ovarian cancer and maintain the key to improve the survival probability. Human leukocyte antigen -E (HLA-E) is a non classical HL A class I molecules, many studies showed that it is involved in tumor immune escape, and many reported high expression in blood and tumor patients. Expression of HLA-E in ovarian serous in literature is rare. So we used immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) on the expression of HLA-E in the SOC method, and to study the role of SOC in pathogenesis and the possibility of SOC as a diagnostic and prognostic index. Objective: the expression of sHLA-E HLA-E cancer patients were detected the expression of SOC and HLA-E in the serum of the patients. The expression and relationship of the parameters between the mechanism and clinical research, HLA-E in the occurrence and development of SOC, compared with the widely used CA125, evaluate the application value of sHLA-E SOC in clinical diagnosis. Methods: the tissue pathology department of Provincial Hospital Affiliated to Shandong University 20 12.07-2015.09 well preserved specimens of SOC were 48 cases, aged 26-72 years old. According to the FIGO2014 staging of ovarian cancer, divided into early (I-II) and late (III-IV), including early and late stage were 18 and 30 respectively. And then selected 12 cases of benign ovarian tumor as control. Blood samples were collected for July 2015 to November 2015 in the Provincial Hospital Affiliated to Shandong University gynecological hospital treatment of serous ovarian cancer, ovarian cyst and uterine fibroids were 42 cases, one group of patients with SOC and patients with benign tumors were 30 cases and 12 cases of.1, the expression of HLA-E in tissue of patients with SOC by immunohistochemical method to detect the expression of HLA-E in 48 cases SOC and 12 cases of benign ovarian tumors, and to evaluate the relationship between the expression of.2 HLA-E in SOC patients and its related clinical parameters, ELISA was used to detect 30 cases of SOC patients and 12 cases of positive expression of sHLA-E in serum of patients with SOC in the Tumor patients (control group) the concentration of serum sHLA-E, sHLA-E concentrations were compared between the two groups in the serum of different subjects, and to compare the correlation between.3 and SOC in patients with clinical parameters, evaluate the application value of sHLA-E in the diagnosis of SOC sHLA-E were compared by ROC curve, the value of CA125 in diagnosis of SOC, and then the testing results of two indexes were compared to evaluate the applied value of sHLA-E in the diagnosis of SOC. Results: 1. Immunohistochemical staining in cell and cell membrane (or cytoplasmic) appear on the Yellow - brown granules showed positive staining intensity and depth, according to the proportion of the total cell evaluation results. The display of HLA-E in tumor tissue SOC positive rate was 72.92% (35/48) was significantly higher than that of benign ovarian tissues with positive rate of 8.3% (1/12), the difference was statistically significant (P0.05).HLA-E expression positive rate and clinical staging. SOC Cut. But.2 is not associated with patient age and tumor differentiation degree, the concentration in the serum of patients with SOC in the mean and standard deviation of 767.03 sHLA-E + 202.19ng/mL while the control group was 616.06 + 86.39ng/mL, SOC serum concentration of sHLA-E was significantly higher than the control group (.3, P0.05) analysis of ROC curve of cut-off value of.SHLA-E with sHLA-E some in the diagnosis of SOC was 631.90 ng/mL, the sensitivity and specificity of 75%. were 78.6% and 1. Conclusion: the expression of HLA-E in tumor tissue and SOC in the serum of the patients was significantly higher than the control group, indicating its occurrence in SOC, there is an important role for.2 development, the sensitivity of sHLA-E in SOC the diagnosis of higher than CA125, but the specificity was lower than CA125, has a potential value in clinical application, has become the possibility of SOC diagnostic indexes.

【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R737.31

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