恶性胸膜间皮瘤基因突变和预后判断的初步研究
发布时间：2019-03-28 16:11
【摘要】：第一部分恶性胸膜间皮瘤基因突变和预后判断的初步研究背景与目的:恶性胸膜间皮瘤(malignant pleural mesothelioma,MPM)是一种来源于胸膜间皮细胞的恶性肿瘤,其以发病隐匿、早期诊断困难、病情进展迅速、预后差为特点。到目前为止,由于此病的相对少见与可供研究的病例相对缺乏,故人们对其此病的发病机理,尤其在其分子、基因层面的认知相对匮乏。我们相信通过对MPM驱动基因的研究有助于我们对此疾病的了解和认识。以往的研究揭示出在MPM患者中存在着基因突变现象,包括NF2、BAP1、CDKN2A、P16、CUL1等,但对于后续的临床治疗的跟踪描述并不完善。随着二代测序技术的出现,我们能够对组织标本进行进一步的大规模的相关基因测序,同时还能够获得基因突变丰度的数据。在我们的研究中,我们收集了18例MPM病理组织切片,进行了二代基因测序,并收集了相关临床数据,希望能够通过基础技术与临床数据相结合,对MPM的基因突变情况及相应的临床特征有更深入的认识,并期望能够最终能转化为对MPM的有效治疗手段。方法:我们共收集了从2006.9-2016.3的18例患者的资料,入组标准在为未接受放化疗的情况下,手术切除或CT引导下穿刺获得标本,经病理诊断为MPM,并且后续均接受了4-6个周期标准联合化疗方案,无其他重大致命性疾病,并剔除了因其他原因致死的患者。我们分别统计了这些病人的性别、初次诊断时的年龄及有无明确的石棉接触史以及根据影像学检查所做的临床分期等相关临床资料。对于这18例已入组的患者,我们于病理科收集到其病理标本,制成石蜡切片,在经过基因提取、浓度测定后,对于符合检测质控标准的标本基因采用燃石朗康?检测技术,对56个相关癌基因进行了二代基因测序(附录1)。检测的项目包括基因名称、突变类型、所在染色体编号、突变丰度等。结果:在本研究中,共收集18例恶性胸膜间皮瘤患者资料。其中,男性11人,女性7人,患者首次确诊年龄在48-84岁之间,平均年龄为(63.9±10.0)岁;15例患者诉有明确的石棉接触暴露史,3例未诉明确的石棉接触暴露史。然后我们依据Butchart分期法,根据患者影像学资料(包括胸部、腹部增强CT,头颅核磁和全身骨扫描)对18例患者进行临床分期,其中Ⅰ期患者共6人,Ⅱ期患者共9人,Ⅲ期患者共3人,Ⅳ期患者0人。我们共检测到发生基因突变的患者为13人,未检测到基因突变的共5人。突变的基因共有20种,包括TP53、FGFR2、NF1、IGF1R、KRAS、FGFR3、SMAD4、APC、TSC2、ERBB2、RET、NTRK3、ERBB4、ARAF、NTRK1、ROS1、SMO1、BRCA1、FGFR3、NRAS。突变的类型包括错义突变、拷贝数异常等。我们对这18位患者分别进行了随访,对每一位患者总生存期进行了统计。我们发现基因突变组总生存时间明显小于未突变组(中位生存期分别为9个月和18个月,p=0.04);在基因突变组中,我们又将TP53基因突变组和TP53野生组进行了总生存期分析,同样发现TP53突变组总生存期少于野生组(中位生存期分别为4.5个月和11.5个月,p=0.01)。结论:我们的研究表明,在纳入本研究的MPM患者中存在着较高基因突变负荷,其中TP53基因突变的这部分患者对治疗效果反应欠佳,预后较差。但由于可收集病例数量限制,有待进一步病例收集和验证。第二部分肺隔离症的诊断与外科治疗的疗效对比目的探讨肺隔离症的诊断方法,并比较传统开胸手术与胸腔镜手术的疗效。方法本文收集了2009-2016年在天津医科大学总医院收治并同意行手术治疗的18例患者临床资料,其中7例行胸腔镜手术,11例行开胸手术。比较两组患者的平均年龄、手术时长、术中出血量、术后引流量、术后引流天数、有无术后并发症、术后住院天数以及总住院费用。结果胸腔镜组术后平均引流时间和住院时间均短于开胸组,差异均有统计学意义(P0.05)(t值分别为4.553和5.068;P0.05)。但两组患者的平均年龄、手术时间、术中出血量总住院费用比较,差异均无统计学意义(P0.05)。其诊断主要依靠胸部影像学诊断,特别是胸部增强CT及三维重建血管成像,能够发现异常动脉血管影,尤其是多排螺旋CT扫描更能明显减少三维重建产生的伪影,使图像更接近于真实,再结合患者既往病史即可初步诊断。结论与传统开胸手术相比,胸腔镜手术的术后引流时间与术后住院时间均更短,说明应用胸腔镜治疗肺隔离症同样安全可靠,而且胸腔镜治疗患者术后恢复更快,伤口美观,值得推广和应用。
[Abstract]:The first part of the study on the mutation and prognosis of malignant pleural mesothelioma (MPM) is a kind of malignant tumor derived from the pleural mesothelioma. The prognosis is a characteristic. So far, since the relatively rare and available cases of this disease are relatively scarce, the pathogenesis of the disease, in particular its molecular and genetic level, is relatively scarce. We believe that the study of the MPM-driven gene will help us to understand and understand this disease. The previous studies have revealed that there is a gene mutation in MPM patients, including NF2, BAP1, CDKN2A, P16, CUL1, etc., but the following description of follow-up clinical treatment is not perfect. With the advent of the second generation sequencing technology, we can carry out a further large-scale related gene sequencing on the tissue specimen, and also can obtain the data of the gene mutation abundance. In our study, we collected 18 MPM pathological tissue sections, carried out second-generation gene sequencing, and collected relevant clinical data. It was hoped to be able to combine the basic technology with clinical data, and to have a better understanding of the gene mutation of the MPM and the corresponding clinical features. And it is desirable to be able to eventually be transformed into an effective means of treatment for mpm. Methods: We collected the data from 18 patients from 2006.9 to 2016.3. The enrollment criteria were obtained by surgical resection or CT-guided puncture under the condition of not receiving the radiotherapy and chemotherapy. The pathological diagnosis was MPM, and 4-6 cycle-standard combined chemotherapy was received in the follow-up. There were no other major fatal diseases and excluded patients who died from other causes. We respectively count on the sex of these patients, the age at the time of the initial diagnosis, the history of exposure to asbestos, and the clinical stage and other relevant clinical data according to the imaging examination. For the 18 enrolled patients, we collected the pathological specimen from the Pathology Section to make the paraffin section. After the gene extraction and concentration measurement, the specimen gene in accordance with the test quality control standard was used to be fired. The second-generation gene sequencing of 56 associated oncogenes was performed using the detection technique (Appendix 1). The items to be tested include gene name, type of mutation, chromosome number, mutation abundance, etc. Results: In this study,18 patients with malignant pleural mesothelioma were collected. Of these,11 males and 7 females, the first diagnosis was between 48 and 84 years, with a mean age of (63.9-10.0) years;15 patients had a clear history of asbestos exposure exposure and 3 did not have a clear history of exposure to asbestos exposure. Then we performed the clinical stage of 18 patients according to the image data of the patient (including the chest, the abdomen enhanced CT, the head core magnetic and the whole body bone scan) according to the Butchart stage method, including 6 patients in stage I,9 in phase II,3 in stage III and 0 in stage 鈪，
本文编号：2449025
[Abstract]:The first part of the study on the mutation and prognosis of malignant pleural mesothelioma (MPM) is a kind of malignant tumor derived from the pleural mesothelioma. The prognosis is a characteristic. So far, since the relatively rare and available cases of this disease are relatively scarce, the pathogenesis of the disease, in particular its molecular and genetic level, is relatively scarce. We believe that the study of the MPM-driven gene will help us to understand and understand this disease. The previous studies have revealed that there is a gene mutation in MPM patients, including NF2, BAP1, CDKN2A, P16, CUL1, etc., but the following description of follow-up clinical treatment is not perfect. With the advent of the second generation sequencing technology, we can carry out a further large-scale related gene sequencing on the tissue specimen, and also can obtain the data of the gene mutation abundance. In our study, we collected 18 MPM pathological tissue sections, carried out second-generation gene sequencing, and collected relevant clinical data. It was hoped to be able to combine the basic technology with clinical data, and to have a better understanding of the gene mutation of the MPM and the corresponding clinical features. And it is desirable to be able to eventually be transformed into an effective means of treatment for mpm. Methods: We collected the data from 18 patients from 2006.9 to 2016.3. The enrollment criteria were obtained by surgical resection or CT-guided puncture under the condition of not receiving the radiotherapy and chemotherapy. The pathological diagnosis was MPM, and 4-6 cycle-standard combined chemotherapy was received in the follow-up. There were no other major fatal diseases and excluded patients who died from other causes. We respectively count on the sex of these patients, the age at the time of the initial diagnosis, the history of exposure to asbestos, and the clinical stage and other relevant clinical data according to the imaging examination. For the 18 enrolled patients, we collected the pathological specimen from the Pathology Section to make the paraffin section. After the gene extraction and concentration measurement, the specimen gene in accordance with the test quality control standard was used to be fired. The second-generation gene sequencing of 56 associated oncogenes was performed using the detection technique (Appendix 1). The items to be tested include gene name, type of mutation, chromosome number, mutation abundance, etc. Results: In this study,18 patients with malignant pleural mesothelioma were collected. Of these,11 males and 7 females, the first diagnosis was between 48 and 84 years, with a mean age of (63.9-10.0) years;15 patients had a clear history of asbestos exposure exposure and 3 did not have a clear history of exposure to asbestos exposure. Then we performed the clinical stage of 18 patients according to the image data of the patient (including the chest, the abdomen enhanced CT, the head core magnetic and the whole body bone scan) according to the Butchart stage method, including 6 patients in stage I,9 in phase II,3 in stage III and 0 in stage 鈪，
本文编号：2449025
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