监测外周血SCF对预测c-kit阳性卵巢癌化疗耐药的临床价值

发布时间：2018-03-12 13:41

本文选题：卵巢上皮性癌　切入点：化疗耐药　出处：《长江大学》2017年硕士论文　论文类型：学位论文

【摘要】：妇科肿瘤是一类常见的女性生殖系统肿瘤,也是人体中的多发肿瘤。据全国2009年恶性肿瘤发病和死亡统计,女性生殖系统恶性肿瘤居发病的前十位,远比男性生殖恶性肿瘤发病率高。卵巢上皮性癌(Epithelial ovarian cancer,EOC)生长方式隐匿,难以早期发现及诊断,约70%的患者发现时即为晚期,卵巢癌死亡率居女性恶性肿瘤首位,因此成为严重威胁女性生命和健康的肿瘤。目前卵巢癌患者的主要治疗方式依赖于手术及化疗,大多数卵巢癌患者对以铂类为主的化疗有较高的反应率,故铂类为主的联合化疗被推荐为卵巢癌的一线化疗方案,但约50%以上的患者复发并产生化疗耐药。晚期患者的5年生存率徘徊在30%左右,卵巢癌的复发和耐药一直是临床上颇为棘手的难题。最近研究发现,c-kit和干细胞因子(stem cell factor,SCF)共同表达对卵巢癌、小细胞肺癌、肝内胆管细胞癌、胃肠间质瘤等发生发展有着非常重要的作用,对化疗药物耐药特别是铂类药物及肿瘤复发均有较大影响,预示着极差的预后。血液中游离的SCF浓度异常或肿瘤细胞SCF和c-kit蛋白表达异常,均可导致酪氨酸激酶信号转导异常,可扰乱生长调控,导致肿瘤形成,对化疗药物特别是铂类药物的耐药及肿瘤复发均有较大影响。目的:本研究拟监测卵巢癌患者外周血中游离干细胞因子(stem cell factor,SCF)的浓度变化和量子点免疫荧光技术检测c-kit蛋白在卵巢癌组织中的表达,探讨外周血SCF值对早期预测c-kit(+)卵巢癌继发性化疗耐药的临床价值。方法:利用量子点(quantum dots,QDs)免疫荧光双染检测106例卵巢癌组织中c-kit和SCF蛋白表达,ELISA法检测46例上述卵巢癌患者化疗期间冰冻保存的外周血SCF值,分析铂类为主的化疗药物敏感型和耐药型卵巢癌患者外周血SCF值与组织c-kit表达的差异。结果:继发性化疗耐药的卵巢癌组织中,c-kit(+)表达率远高于化疗敏感组(29.27%vs 10.8%,p0.05),c-kit(+)表达率随着FIGO分期的进展而升高(I-II期8.7%,III-IV期25%,p0.05)。继发性化疗耐药组的外周血SCF值随铂类为主的化疗药物治疗而有升高的趋势,化疗敏感组的SCF值随之有下降的趋势;继发性化疗耐药组的外周血SCF均值高于化疗敏感组(p0.05)。卵巢癌c-kit(+)的外周血SCF值均值高于c-kit(-)组(p=0.018),外周血SCF值在卵巢癌c-kit(+)组随铂类为主的化疗耐药而升高。结论:卵巢上皮癌组织中c-kit蛋白阳性表达可能导致肿瘤对铂类化疗药物耐药;c-kit蛋白在肿瘤间质细胞内的阳性表达,预示卵巢上皮性癌化疗耐药微环境的形成和极差的临床结局。卵巢癌化疗期间,监测外周血SCF值升高可能是早期预测c-kit(+)卵巢癌继发性化疗耐药的标记物之一。
[Abstract]:Gynecological tumor is a kind of common female reproductive system tumor, and it is also the multiple tumor in human body. According to the statistics of incidence and death of malignant tumor in 2009 in China, female reproductive system malignant tumor occupies the top ten in the incidence of malignant tumor. The incidence of ovarian epithelial ovarian cancer (EOC) is far higher than that of male reproductive malignancies. The growth pattern of epithelial ovarian cancer of ovary is hidden, and it is difficult to detect and diagnose early. About 70% of the patients are advanced when found, and the mortality rate of ovarian cancer is the highest in female malignant tumors. At present, most ovarian cancer patients rely on surgery and chemotherapy. Most ovarian cancer patients have a high response rate to platinum-based chemotherapy. Therefore, platinum-based combination chemotherapy is recommended as a first-line chemotherapy regimen for ovarian cancer, but more than 50% of the patients relapse and develop chemotherapeutic resistance. The 5-year survival rate of advanced patients hovers around 30%. The recurrence and resistance of ovarian cancer has been a difficult clinical problem. Recent studies have found that c-kit and stem cell factor-SCFs co-express in ovarian cancer, small cell lung cancer, and intrahepatic cholangiocarcinoma. Gastrointestinal stromal tumors (GIST) play an important role in the occurrence and development of gastrointestinal stromal tumors, and have great influence on chemotherapeutic drug resistance, especially platinum drugs and tumor recurrence. Abnormal concentrations of free SCF in blood or abnormal expression of SCF and c-kit protein in tumor cells can lead to abnormal signal transduction of tyrosine kinase, which can disrupt growth regulation and lead to tumor formation. Objective: the aim of this study was to monitor the concentration of free stem cell factor stem cell factor in peripheral blood of patients with ovarian cancer and the quantum dot immunofluorescence technique. To detect the expression of c-kit protein in ovarian cancer, To investigate the clinical value of peripheral blood SCF value in early prediction of secondary chemotherapeutic resistance of c-kitc () ovarian cancer. Methods: the expression of c-kit and SCF protein was detected by Elisa in 46 cases of ovarian cancer by using quantum dot quantum dot quantum Dot (quantum Dot) immunofluorescence double staining method to detect the expression of c-kit and SCF protein in 106 cases of ovarian cancer. The SCF values of cryopreserved peripheral blood of ovarian cancer patients during chemotherapy were described. The difference of SCF and c-kit expression in peripheral blood of patients with chemotherapy-sensitive and drug-resistant ovarian cancer was analyzed. Results: the expression rate of c-kitc () in chemotherapy-resistant ovarian cancer was much higher than that in chemosensitive group (29.27 vs 10.8 p0.05). The expression rate increased with the progress of FIGO stage, and increased with the advance of FIGO staging. The level of SCF in peripheral blood of patients with secondary chemotherapeutic resistance increased with the treatment of platinum-based chemotherapeutic drugs. The SCF value of chemotherapy-sensitive group decreased. The mean value of SCF in peripheral blood of patients with secondary chemotherapeutic resistance was higher than that of chemotherapy-sensitive group (P 0.05). The mean value of SCF in peripheral blood of ovarian cancer was higher than that of c-kita-group. The SCF value of peripheral blood in patients with ovarian cancer was higher than that in patients with chemotherapeutic resistance. Conclusion:. The positive expression of c-kit protein in epithelial ovarian carcinoma may lead to the positive expression of c-kit protein in tumor stromal cells. During the chemotherapy of ovarian cancer, monitoring the increase of peripheral blood SCF value may be one of the early markers for predicting the secondary chemotherapeutic resistance of c-kitc () ovarian cancer.
【学位授予单位】：长江大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.31

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