血液、唾液中IEX-1水平检测在卵巢恶性肿瘤中的诊断价值

发布时间：2018-06-19 09:17

本文选题：即刻早期反应基因-1(IEX-1) + 卵巢恶性肿瘤　；参考：《郑州大学》2014年硕士论文

【摘要】：背景和目的卵巢恶性肿瘤是妇科三大恶性肿瘤之一，由于位置深在，缺乏早期症状，70%患者诊断时已属晚期，虽行肿瘤细胞减灭术及化疗，晚期患者5年生存率仅为20-30%。血清肿瘤标志物的检测在辅助卵巢癌临床诊断，化疗效果检测，预后判定方面发挥了重要作用，但仍存在着特异度和灵敏度不高的问题，因此，寻找一种更加灵敏有效的肿瘤标志物具有重要的意义。即刻早期反应基因（immediate early response gene X-1,IEX-1）在调节细胞凋亡、增殖、分化中发挥了一个关键的作用，在人类的多种肿瘤中已经证实，依赖于肿瘤类型和发展阶段，IEX-1的异常表达和肿瘤的预后密切相关。我们前期的研究也发现：IEX-1在卵巢上皮性肿瘤中的表达和凋亡指数二者呈正相关,生存分析发现，IEX-1阳性表达的患者与较高的生存率有关，提示IEX-1可能发挥着某种抑癌的作用，提示IEX-1可以作为卵巢癌的预后因子，但有关其诊断价值却鲜有报道。血液是最常用的临床上检测肿瘤标志物的样本；唾液作为一种无创的、较易获得的生物学标本，当机体发生某种疾病时，唾液中某些成分会发生变化，血液中发生变化的某些生物标志物在唾液中也可检测到，使唾液作为标本用于疾病的诊断成为可能。方法本研究收集26例卵巢恶性肿瘤、37例盆腔良性疾病病人及55例健康妇女的血液及唾液标本，分别提取RNA，采用实时荧光定量PCR法探讨唾液及血液中IEX-1的表达水平，并应用受试者工作特征(ROC)曲线分析IEX-1在诊断和鉴别卵巢恶性肿瘤的敏感度、特异度及准确度，探讨IEX-1作为肿瘤标志物在诊断卵巢癌中的价值。结果 1.盆腔良性疾病组、健康对照组血液中IEX-1的表达水平均明显高于卵巢恶性肿瘤组，分别为（1.81±0.31）、（1.72±0.32）倍，差异有统计学意义（p0.017）；唾液中盆腔良性疾病组、健康对照组血液中IEX-1的表达水平均明显高于卵巢恶性肿瘤组，，分别为（1.67±0.37）、（1.80±0.40）倍，差异有统计学意义（p0.017）；盆腔良性疾病组及健康对照组比较，全血和唾液中IEX-1表达差异均无统计学意义(p0.017)； 2.血液中，卵巢恶性肿瘤组分别以卵巢良性肿瘤组、健康对照组为参照时，IEX-1检测的曲线下面积(AUC)分别为0.947、0.929。IEX-1在鉴别卵巢恶性肿瘤组与盆腔良性疾病组中的灵敏度和特异度分别为84.6%、94.6%，在鉴别卵巢恶性肿瘤组与健康对照组中的灵敏度和特异度分别为84.6%，90.9%； 3.唾液中，卵巢恶性肿瘤组分别以卵巢良性肿瘤组、健康对照组为参照时，IEX-1检测的AUC分别为0.851、0.896。IEX-1在鉴别卵巢恶性肿瘤组与盆腔良性疾病组中的灵敏度和特异度分别为65.4%，94.6%，在鉴别卵巢恶性肿瘤组与健康对照组中的灵敏度和特异度分别为92.3%，72.5%。结论 1.唾液中可以提取出来完整且足量的RNA，能够满足荧光定量PCR的需要； 2.血液中IEX-1的表达水平检测对卵巢恶性肿瘤诊断具有较高的诊断效能，唾液中IEX-1的表达水平检测对卵巢恶性肿瘤具有中等的诊断效能； 3.唾液因其技术无创性及和标本采集方便等特点,可能成为新的临床诊断标本。
[Abstract]:Background and purpose
Ovarian malignant tumor is one of the three major malignant tumors in gynecology. Because of its deep location and lack of early symptoms, 70% patients are advanced in diagnosis. Although tumor cell subtraction and chemotherapy are performed, the 5 year survival rate of advanced patients is only 20-30%. serum tumor markers in the clinical diagnosis of ovarian cancer, the detection of chemotherapy and the prognosis. It plays an important role, but there is still a problem of specificity and sensitivity. Therefore, it is of great significance to find a more sensitive and effective tumor marker. The immediate early response gene (immediate early response gene X-1, IEX-1) plays a key role in regulating apoptosis, proliferation and differentiation. The abnormal expression of IEX-1 is closely related to the prognosis of the tumor in the tumor type and development stage. Our previous study also found that the expression of IEX-1 in epithelial ovarian tumors was positively correlated with the apoptotic index two. Survival analysis found that the patients with IEX-1 positive expression were related to the higher survival rate. IEX-1 may play a certain role in suppressing cancer, suggesting that IEX-1 can be used as a prognostic factor for ovarian cancer, but the diagnostic value of it is rarely reported. Blood is the most commonly used sample of clinical detection of tumor markers; saliva is a noninvasive, more readily available biological specimen, when a certain disease occurs in the body, and some of the saliva is in the saliva. Some of the ingredients will change, and some of the biomarkers in the blood can be detected in saliva, making it possible for saliva to be used as a specimen for the diagnosis of disease.
Method
In this study, 26 cases of ovarian malignant tumor, 37 cases of benign pelvic diseases and 55 healthy women's blood and saliva specimens were collected, RNA was extracted respectively. The expression of IEX-1 in saliva and blood was studied by real-time fluorescence quantitative PCR method. The sensitivity of IEX-1 in the diagnosis and identification of malignant ovarian tumors was analyzed by using the working characteristics of the subjects (ROC). The sensitivity, specificity and accuracy of IEX-1 as a tumor marker in the diagnosis of ovarian cancer were discussed.
Result
1. the expression level of IEX-1 in the healthy control group was significantly higher than that of the ovarian malignant tumor group (1.81 + 0.31), (1.72 + 0.32) times (1.72 + 0.32), and the difference was statistically significant (p0.017). The expression level of IEX-1 in the healthy control group of the saliva was significantly higher than that of the ovarian malignant tumor group, respectively. (1.67 + 0.37), (1.80 + 0.40) times, the difference was statistically significant (p0.017); there was no significant difference in the expression of IEX-1 in both the whole blood and the saliva between the benign and healthy control group (p0.017).
2. in the blood, the ovarian malignant tumor group was treated with the benign ovarian tumor group and the healthy control group. The area under the curve of IEX-1 detection (AUC) was respectively 0.947,0.929.IEX-1 in the identification of the ovarian malignant tumor group and the pelvic benign disease group, the sensitivity and specificity were 84.6%, 94.6%, respectively, in the identification of ovarian malignant tumor group and healthy control. The sensitivity and specificity of the group were 84.6% and 90.9% respectively.
In the 3. saliva, the ovarian malignant tumor group was treated with the benign ovarian tumor group and the healthy control group. The sensitivity and specificity of IEX-1 detected by AUC were 65.4% and 94.6% respectively in the identification of ovarian malignant tumor group and the pelvic benign disease group, respectively, and the sensitivity of the ovarian malignant tumor group was sensitive to the healthy control group and the healthy control group. The degree and specificity are 92.3%, 72.5%.
conclusion
1. full and sufficient RNA can be extracted from saliva to meet the needs of fluorescent quantitative PCR.
2. the expression level of IEX-1 in the blood has a high diagnostic efficiency for the diagnosis of ovarian malignant tumor. The detection of IEX-1 expression level in saliva has medium diagnostic efficiency for ovarian malignant tumor.
3. saliva may be a new clinical diagnostic specimen because of its non-invasive technology and convenient specimen collection.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R737.31

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