ERCC1、RRM1在肺腺癌、鳞癌中的表达及与预后关系的研究

发布时间：2018-05-06 15:38

本文选题：非小细胞肺癌 + ERCCl　；参考：《大连医科大学》2015年硕士论文

【摘要】：背景肺癌是常见恶性肿瘤,近年来肺癌的发病率及死亡率逐渐上升,2014年全世界肺癌新发病例约占所有新发恶性肿瘤的14%,约占所有恶性肿瘤死亡率的25%,为全球死亡率最高的肿瘤之一[1],而其中非小细胞肺癌(non-small cell lung cancer,NSCLC)患者约占到80%[2]。新确诊的非小细胞肺癌患者中仅有25%可手术治疗,化疗仍为主要治疗方式,虽然术后辅助化疗能提高4%的5年生存率,但仍有部分患者出现复发和转移,如何筛选术后辅助化疗有效或无效的病例成为医学难题。因此,越来越多人认为NSCLC患者的术后辅助治疗应在判定分子标志物基础上指导术后辅助化疗药物的个体化治疗选择。近些年,分子生物技术的进步、分子生物学研究的深入,更多的与肿瘤发生发展关系密切的肿瘤标记物被发现,肿瘤的个体化治疗也越来越被人们接受。切除修复交叉互补基因1(excision repair cross complementation 1,ERCCl)、核糖核苷酸还原酶Ml(ribonucleotide reductase 1,RRMl)在肿瘤组织中常常表达,其表达水平可能与治疗某些化疗药物的疗效相关,所以可作为非小细胞肺癌个体化治疗中指导治疗常用的肿瘤分子标记物,多项已发表的研究证实,ERCC1的表达水平与铂类药物疗效相关,高表达的ERCC1水平可能意味着铂类原发性耐药,即若ERCC1低表达,则对铂类药物敏感;而肿瘤组织中RRM1蛋白的表达与患者对吉西他滨的敏感性相关,若RRM1蛋白表达低,则患者对吉西他滨药物敏感。目的检测非小细胞肺癌(non small cell lung cancer,NSCLC)患者,主要为肺腺癌和鳞癌患者,标本均为手术切除标本,检测相应标本的ERCCl和RRMl的蛋白表达水平,探讨ERCC1、RRM1蛋白表达水平与非小细胞肺癌术后吉西他滨联合顺铂(GP)辅助化疗预后的关系,指导临床个体化治疗。方法随访49例临床IIA-IIIA期接受手术治疗的NSCLC患者,所有患者在术前均未接受任何对肿瘤的治疗措施,术后均接受4个周期以上化疗。采用免疫组化方法检测ERCC1、RRM1表达,并统计分析患者不同的临床特征、病理特征、术后治疗方式、ERCCl/RRMl蛋白表达对无疾病进展期的影响。Cox回归分析筛选影响预后的独立危险因子,Kaplan-Meier生存曲线分析比较各组患者的无进展生存期及总生存时间。结果1、ERCC1蛋白表达结果:在49例样本中,21例为阳性;RRM1蛋白表达结果:30例为阳性。采用免疫组化方法对49例患者肿瘤组织样本中的ERCC1和RRM1蛋白的表达进行测定,结果发现NSCLC组织样本中ERCC1、RRM1蛋白表达水平与患者各临床病理参数,如:病理类型、分期、淋巴结转移状况无关。2、总生存状况:术后患者ERCC1不表达组优于ERCC1表达组,两组间中位无进展生存期及中位总生存期具有显著性差异(15.2m VS 12.5m,P=0.038;18.6m VS 16.8m,P=0.037)。3、总生存状况:术后患者RRM1不表达组优于RRM1表达组,两组间中位无进展生存期及中位总生存期差异均具有显著性(14.6月VS11.5月,P=0.048;18.6月VS17.8月,P=0.04)。结论1、NSCLC样本中的ERCC1蛋白表达水平与病理分期、淋巴结转移情况和组织病理类型无关。2、NSCLC样本中的RRM1蛋白表达与病理分期、淋巴结转移情况及组织病理类型无关。3、ERCC1表达阴性的NSCLC IIA-IIIA期患者对含铂化疗方案敏感,生存优势大于高表达者;而RRM1表达阴性NSCLC IIA-IIIA期患者对化疗药吉西他滨敏感,生存优势大于高表达者。ERCC1及RRM1表达水平可作为评估患者应用GP方案化疗后生存预后的重要预测因子。
[Abstract]:Background lung cancer is a common malignant tumor. In recent years, the incidence and mortality of lung cancer are increasing gradually. In 2014, new cases of lung cancer in the world accounted for about 14% of all new malignant tumors, accounting for 25% of all malignant tumor mortality, one of the [1] of the highest mortality in the world, and non small cell lung cancer (non-small cell lung cancer, NSCL) C) only 25% of the patients with 80%[2]. newly diagnosed non-small cell lung cancer are operated on, and chemotherapy is still the main treatment. Although adjuvant chemotherapy can increase the 5 year survival rate of 4%, there are still some patients with recurrence and metastasis. How to screen the effective or invalid cases of adjuvant chemotherapy becomes a medical problem. The more people think that the postoperative adjuvant therapy for NSCLC patients should be selected on the basis of molecular markers to guide the individualized treatment of adjuvant chemotherapy drugs. In recent years, the progress of molecular biotechnology, the in-depth study of molecular biology, the discovery of more closely related tumor markers, and the individualization of tumor. Treatment is also getting more and more accepted. Resection and repair of cross complementary gene 1 (excision repair cross complementation 1, ERCCl), ribonucleotide reductase Ml (ribonucleotide reductase 1, RRMl) are often expressed in tumor tissues, and the expression level may be related to the therapeutic effect of some chemotherapeutic drugs, so it can be used as a non small cell lung. A number of published studies have confirmed that the expression level of ERCC1 is associated with the efficacy of platinum drugs. The high expression of ERCC1 may mean platinum type primary drug resistance, that is, the sensitivity to platinum drugs if ERCC1 is low expression, and the expression of RRM1 protein in tumor tissues is associated with patients. The sensitivity of gemcitabine is related. If RRM1 protein is low, the patient is sensitive to gemcitabine. Objective to detect non small cell lung cancer (non small cell lung cancer, NSCLC), mainly for lung adenocarcinoma and squamous cell carcinoma. All specimens are surgically excised, and the protein expression level of ERCCl and RRMl in the corresponding specimens is detected, ERCC1, RRM1. The protein expression level is associated with the prognosis of gemcitabine combined with cisplatin (GP) adjuvant chemotherapy after the operation of non small cell lung cancer (non-small cell lung cancer), guiding clinical individualized treatment. Methods follow up 49 patients with NSCLC patients undergoing surgical treatment at IIA-IIIA stage. All patients received no treatment for tumor before operation, and all patients received more than 4 cycles of chemotherapy after operation. Immunohistochemical method was used to detect ERCC1, RRM1 expression and statistical analysis of patients with different clinical features, pathological features, postoperative treatment, and the effect of ERCCl/RRMl protein expression on progression free progression by.Cox regression analysis and screening of independent risk factors affecting prognosis. Kaplan-Meier survival curve analysis was used to compare the progression free survival period of the patients in each group. And total survival time. Results 1, ERCC1 protein expression results: in 49 samples, 21 cases were positive; RRM1 protein expression results: 30 cases were positive. Immunohistochemical method was used to determine the expression of ERCC1 and RRM1 protein in the tumor tissue samples of 49 patients. The results showed that the expression level of ERCC1, RRM1 protein in the NSCLC tissue samples and the patients were in the presence of each of the patients. Pathological parameters of bed, such as pathological type, staging, lymph node metastasis were not related to.2, total survival status: the ERCC1 non expression group after operation was superior to ERCC1 expression group, and there was a significant difference between the two groups in the median progression free survival and the median survival period (15.2m VS 12.5m, P=0.038; 18.6m VS 16.8m, P=0.037).3, the total survival status: postoperative patients did not watch The group was superior to the RRM1 expression group. The difference between the two groups was significant (14.6 months VS11.5, P=0.048, 18.6 month VS17.8, P=0.04). Conclusion 1, the expression level of ERCC1 protein in the NSCLC sample is not related to pathological stage, lymph node metastasis and histopathological type.2, RRM1 protein in NSCLC sample Expression and pathological staging, lymph node metastasis and histopathological types were not related to.3, ERCC1 negative NSCLC IIA-IIIA patients were sensitive to platinum chemotherapy, survival advantage was greater than high expression, and RRM1 expression negative NSCLC IIA-IIIA patients were sensitive to chemotherapy drug gemcitabine, survival advantage was greater than high expression of.ERCC1 and RRM1 expression. The level can be used as an important predictor of survival prognosis after GP chemotherapy.

【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R734.2

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