颅内生殖细胞肿瘤的临床资料和差异蛋白质组学研究

发布时间：2018-04-09 16:57

  本文选题：颅内生殖细胞肿瘤　切入点：激光显微切割　出处：《北京协和医学院》2016年博士论文

【摘要】：背景：中枢性尿崩症(central diabetes insipidus, CDI)是神经外科和内分泌科常见症状之一,其中33%-37%中枢性尿崩患者MRI表现为垂体柄增粗。中枢性尿崩症合并垂体柄增粗的病因有很多种,尤以生殖细胞瘤的恶性程度最高、病情发展最快、预后最差。颅内生殖细胞瘤(intracranial germ cell tumors, icGCTs)属低度恶性肿瘤,多呈浸润性生长,常有不同程度和形式的转移。目前术前较难明确诊断,活检病理为金标准；然而脑组织活检具有创伤大、病人依从性差、术后并发症多、手术难度大、护理限制因素多等问题。为减轻患者痛苦,我们旨在应用蛋白质组学的方法寻找与颅内生殖细胞瘤诊断相关的信号传导通路和疾病标志物,从而提供无创检测生殖细胞瘤的一种新途径。目的：1、总结icGCT的临床特性,分析icGCT的预后影响因素；2、应用蛋白质组学的方法寻找与颅内生殖细胞瘤诊断相关的信号传导通路和疾病标志物,从而提供无创检测生殖细胞瘤的一种新途径。方法：1、回顾性总结分析2008年9月-2015年12月在北京协和医院收治的具有完整临床资料并经病理结果证实的颅内生殖细胞瘤肿瘤患者73例的临床资料,其中随访病人66例；2、收集北京协和医院2012年8月-2014年8月期间收治的8例纯生殖细胞肿瘤的福尔马林固定石蜡包埋组织标本,利用激光显微切割(laser micro-dissection,LMD)的方式采集肿瘤组织后,利用液相色谱串联质谱(liquid chromatography combined with mass spectrometray,LC/MS)方法寻找肿瘤组／肿瘤旁组和肿瘤组／对照组的差异蛋白质。结果：1、肿瘤最大直径≥15mm的颅内生殖细胞肿瘤患者发生预后不良危险是直径15mm的8.96倍(2.54-31.66)；免疫组化OCT阳性的颅内生殖细胞肿瘤患者发生预后不良危险是OCT阴性的4.33倍(1.18-15.89)；非生殖细胞瘤性生殖细胞肿瘤患者(nongerminomatous germ cell tumors,NGGCT)发生预后不良危险是纯生殖细胞瘤的6.56倍(1.62-26.58)；采用联合放化疗治疗的颅内生殖细胞肿瘤患者发生预后不良危险是未联合放化疗的0.20倍(0.06-0.67)。2、肿瘤组／肿瘤旁组的差异蛋白175个,均为上调蛋白,参与42条相关信号通路；肿瘤组／对照组差异蛋白45个,其中上调蛋白38个,下调蛋白7个,参与33条相关信号通路。结论：1、肿瘤最大直径≥15mm、免疫组化OCT染色阳性、病理分型为NGGCT是颅内生殖细胞肿瘤患者预后的危险因素；采用联合放化疗是颅内生殖细胞肿瘤患者预后的保护因素。2、e1F2信号传导通路和PI3K/Akt信号转导通路有可能在颅内纯生殖细胞瘤的发生和发展中发挥重要作用。
[Abstract]:Background: central diabetes insipidus (CDII) is one of the common symptoms in neurosurgery and endocrine department. Among them, 33% to 37% of the patients with central diabetes insipidus showed thickening of pituitary stalk on MRI.There are many causes of central diabetes insipidus with thickening pituitary stalk, especially germinoma has the highest malignant degree, the fastest development and the worst prognosis.Intracranial germ cell tumors (icGCTs) are low grade malignant tumors, which are usually infiltrative and often metastasized in different degrees and forms.At present, it is difficult to make a definite diagnosis before operation, and biopsy pathology is the golden standard. However, brain biopsy has many problems, such as big trauma, poor patient compliance, more postoperative complications, more difficult operation, more nursing restrictive factors and so on.In order to alleviate the suffering of patients, we aim to search for signal transduction pathways and disease markers related to the diagnosis of intracranial germinoma by using proteomics, which provides a new non-invasive approach for the detection of germinoma.Objective to summarize the clinical characteristics of icGCT, analyze the prognostic factors of icGCT and find the signal transduction pathways and disease markers related to the diagnosis of intracranial germinoma by proteomics.This provides a new noninvasive approach for the detection of germ cell tumor.Methods: the clinical data of 73 patients with intracranial germ cell tumor confirmed by pathology from September 2008 to December 2015 in Peking Union Hospital were analyzed retrospectively.Among them, 66 cases were followed up. The specimens of formalin fixed paraffin embedded tissue from 8 cases of pure germ cell tumor treated in Beijing Union Hospital from August 2012 to August 2014 were collected by laser micro-dissection LMD-LMD-method.Liquid chromatography-tandem mass spectrometry (LC-MS) was used to search for differential proteins in tumor group / paraneoplastic group and tumor group / control group by liquid chromatography-tandem mass spectrometry (LC-MS).Results the risk of poor prognosis in patients with intracranial germ cell tumors with the largest diameter of 15mm 鈮，

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