本文選題：顱內(nèi)生殖細(xì)胞腫瘤　切入點(diǎn)：激光顯微切割　出處：《北京協(xié)和醫(yī)學(xué)院》2016年博士論文

【摘要】：背景：中樞性尿崩癥(central diabetes insipidus, CDI)是神經(jīng)外科和內(nèi)分泌科常見(jiàn)癥狀之一,其中33%-37%中樞性尿崩患者M(jìn)RI表現(xiàn)為垂體柄增粗。中樞性尿崩癥合并垂體柄增粗的病因有很多種,尤以生殖細(xì)胞瘤的惡性程度最高、病情發(fā)展最快、預(yù)后最差。顱內(nèi)生殖細(xì)胞瘤(intracranial germ cell tumors, icGCTs)屬低度惡性腫瘤,多呈浸潤(rùn)性生長(zhǎng),常有不同程度和形式的轉(zhuǎn)移。目前術(shù)前較難明確診斷,活檢病理為金標(biāo)準(zhǔn)；然而腦組織活檢具有創(chuàng)傷大、病人依從性差、術(shù)后并發(fā)癥多、手術(shù)難度大、護(hù)理限制因素多等問(wèn)題。為減輕患者痛苦,我們旨在應(yīng)用蛋白質(zhì)組學(xué)的方法尋找與顱內(nèi)生殖細(xì)胞瘤診斷相關(guān)的信號(hào)傳導(dǎo)通路和疾病標(biāo)志物,從而提供無(wú)創(chuàng)檢測(cè)生殖細(xì)胞瘤的一種新途徑。目的：1、總結(jié)icGCT的臨床特性,分析icGCT的預(yù)后影響因素；2、應(yīng)用蛋白質(zhì)組學(xué)的方法尋找與顱內(nèi)生殖細(xì)胞瘤診斷相關(guān)的信號(hào)傳導(dǎo)通路和疾病標(biāo)志物,從而提供無(wú)創(chuàng)檢測(cè)生殖細(xì)胞瘤的一種新途徑。方法：1、回顧性總結(jié)分析2008年9月-2015年12月在北京協(xié)和醫(yī)院收治的具有完整臨床資料并經(jīng)病理結(jié)果證實(shí)的顱內(nèi)生殖細(xì)胞瘤腫瘤患者73例的臨床資料,其中隨訪病人66例；2、收集北京協(xié)和醫(yī)院2012年8月-2014年8月期間收治的8例純生殖細(xì)胞腫瘤的福爾馬林固定石蠟包埋組織標(biāo)本,利用激光顯微切割(laser micro-dissection,LMD)的方式采集腫瘤組織后,利用液相色譜串聯(lián)質(zhì)譜(liquid chromatography combined with mass spectrometray,LC/MS)方法尋找腫瘤組／腫瘤旁組和腫瘤組／對(duì)照組的差異蛋白質(zhì)。結(jié)果：1、腫瘤最大直徑≥15mm的顱內(nèi)生殖細(xì)胞腫瘤患者發(fā)生預(yù)后不良危險(xiǎn)是直徑15mm的8.96倍(2.54-31.66)；免疫組化OCT陽(yáng)性的顱內(nèi)生殖細(xì)胞腫瘤患者發(fā)生預(yù)后不良危險(xiǎn)是OCT陰性的4.33倍(1.18-15.89)；非生殖細(xì)胞瘤性生殖細(xì)胞腫瘤患者(nongerminomatous germ cell tumors,NGGCT)發(fā)生預(yù)后不良危險(xiǎn)是純生殖細(xì)胞瘤的6.56倍(1.62-26.58)；采用聯(lián)合放化療治療的顱內(nèi)生殖細(xì)胞腫瘤患者發(fā)生預(yù)后不良危險(xiǎn)是未聯(lián)合放化療的0.20倍(0.06-0.67)。2、腫瘤組／腫瘤旁組的差異蛋白175個(gè),均為上調(diào)蛋白,參與42條相關(guān)信號(hào)通路；腫瘤組／對(duì)照組差異蛋白45個(gè),其中上調(diào)蛋白38個(gè),下調(diào)蛋白7個(gè),參與33條相關(guān)信號(hào)通路。結(jié)論：1、腫瘤最大直徑≥15mm、免疫組化OCT染色陽(yáng)性、病理分型為NGGCT是顱內(nèi)生殖細(xì)胞腫瘤患者預(yù)后的危險(xiǎn)因素；采用聯(lián)合放化療是顱內(nèi)生殖細(xì)胞腫瘤患者預(yù)后的保護(hù)因素。2、e1F2信號(hào)傳導(dǎo)通路和PI3K/Akt信號(hào)轉(zhuǎn)導(dǎo)通路有可能在顱內(nèi)純生殖細(xì)胞瘤的發(fā)生和發(fā)展中發(fā)揮重要作用。
[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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