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人類白細胞抗原-E在漿液性卵巢癌患者中的表達及臨床應用研究

發(fā)布時間:2018-01-02 01:01

  本文關鍵詞:人類白細胞抗原-E在漿液性卵巢癌患者中的表達及臨床應用研究 出處:《山東大學》2016年碩士論文 論文類型:學位論文


  更多相關文章: HLA-E sHLA-E 漿液性卵巢癌 CA125


【摘要】:背景:卵巢的惡性腫瘤是女性生殖系統(tǒng)最常見的惡性腫瘤之一,在每個年齡段中均有發(fā)病,而上皮性腫瘤好發(fā)于50歲以后的婦女,5年生存率一直處于30%到40%之間,死亡率均高于其他婦科惡性腫瘤,位于第一位,已經(jīng)成了對女性身體健康和生存影響最大的腫瘤之一。在上皮性卵巢癌中漿液性卵巢癌(SOC)占75%,其5年的生存率卻很低僅為30.6%。目前仍缺乏簡便實用而敏感性特異性高的診斷方法,大部分患者就診時已錯過手術(shù)的最佳時期發(fā)展到臨床晚期。所以及早篩查、及早發(fā)現(xiàn)、及早診斷、及早治療是卵巢癌患者維持生命質(zhì)量和提高生存概率的關鍵。人類白細胞抗原-E (HLA-E)是一種非經(jīng)典的HLA I類分子,很多研究表明其參與腫瘤的免疫逃逸,并且很多文獻報道其在多種腫瘤組織和腫瘤患者血液中出現(xiàn)高表達。關于HLA-E在漿液性卵巢中表達的文獻少見。所以我們應用免疫組化和酶聯(lián)免疫吸附試驗(ELISA)的方法研究HLA-E在SOC中的表達,以探討其在SOC發(fā)病機制中的作用及作為SOC診斷和預后指標的可能性。目的:檢測SOC患者癌組織中HLA-E的表達和患者血清中sHLA-E的表達。比較HLA-E的表達與腫瘤臨床各相關參數(shù)間的關系,從而研究HLA-E在SOC的發(fā)生與發(fā)展中的機制,同已廣泛應用的CA125進行比較,評價sHLA-E在SOC臨床診斷中的應用價值。方法:切片組織為山東大學附屬省立醫(yī)院病理科2012.07-2015.09保存完好的SOC標本共48例,年齡為26-72歲。根據(jù)FIGO2014卵巢癌分期標準,分成早期(Ⅰ-Ⅱ)和晚期(Ⅲ-Ⅳ),其中早期和晚期分別為18和30例。然后再選取12例卵巢良性腫瘤做為對照。血標本為2015年7月到2015年11月在山東大學附屬省立醫(yī)院婦科住院治療的漿液性卵巢癌、卵巢囊腫和子宮肌瘤患者共42例,其中SOC患者和良性腫瘤患者組分別為30例和12例。1、SOC患者組織中HLA-E的表達采用免疫組化的方法來檢測48例SOC和12例卵巢良性腫瘤組織中HLA-E的表達情況,并評價SOC患者中HLA-E的表達情況與其臨床相關參數(shù)之間的關系。2, sHLA-E在SOC患者血清中的表達應用ELISA法檢測30例SOC患者和12例良性腫瘤患者(對照組)血清中sHLA-E的濃度,對比兩組研究對象血清中sHLA-E濃度的不同,并比較其與SOC患者的臨床相關參數(shù)之間的相關性。3、評價sHLA-E在SOC診斷中的應用價值 通過ROC曲線分別比較sHLA-E、CA125對SOC的診斷價值,然后將兩個指標的檢測結(jié)果進行比較,評價sHLA-E在SOC診斷中的應用價值。結(jié)果:1、免疫組織化學染色后在細胞的胞膜和(或)胞漿上出現(xiàn)黃-棕色顆粒顯示結(jié)果陽性,根據(jù)染色深淺強度和細胞占整體的比例進行綜合評分。結(jié)果顯示HLA-E在SOC腫瘤組織中陽性率為72.92%(35/48)明顯高于卵巢良性組織中的陽性率8.3%(1/12),差異有統(tǒng)計學意義(P0.05)。HLA-E表達的陽性率與SOC的臨床分期密切相關。但與患者年齡和腫瘤分化程度無關。2、sHLA-E在SOC患者血清中濃度均值和標準差為767.03±202.19ng/mL而對照組患者則為616.06±86.39ng/mL, SOC患者血清中sHLA-E濃度明顯高于對照組(P0.05)。3、分析ROC曲線知sHLA-E在SOC的診斷中具有一定的價值。sHLA-E的截點值為631.90 ng/mL,其診斷的特異性和敏感性分別為:78.6%和75%。結(jié)論:1、HLA-E在SOC腫瘤組織和患者血清中的表達明顯高于對照組,說明其在SOC的發(fā)生、發(fā)展中有重要的作用。2、sHLA-E在SOC診斷中的敏感性高于CA125,但特異性卻低于CA125,具有一定潛在的臨床應用價值,有成為SOC診斷指標的可能性。
[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.

【學位授予單位】:山東大學
【學位級別】:碩士
【學位授予年份】:2016
【分類號】:R737.31

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