發(fā)布時間：2018-02-28 20:21

  本文關(guān)鍵詞： GBM 生物信息學(xué) Fibulin-4 IGFBP-2 CH3L1 預(yù)后　出處：《吉林大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：背景:GBM是成人中樞神經(jīng)系統(tǒng)最常見且是惡性程度最高的腦腫瘤,盡管采用包括手術(shù)切除、術(shù)后放射治療以及替莫唑胺化療的標(biāo)準(zhǔn)治療方案,但大多數(shù)病人預(yù)后仍差。一小部分患者預(yù)后相對較好,中位生存期達(dá)到24個月或更長時間。研究發(fā)現(xiàn)GBM病人對各種治療的敏感性以及預(yù)后情況受多種分子標(biāo)記物的影響。尋找與GBM預(yù)后相關(guān)的因素對提高患者生存率有重大意義。生物信息技術(shù)可以對數(shù)據(jù)庫中的大量微陣列數(shù)據(jù)進(jìn)行同源性分析、相似性分析等等,使我們在全基因水平研究基因的調(diào)控,因此,生物信息技術(shù)的應(yīng)用大大促進(jìn)了醫(yī)學(xué)基礎(chǔ)研究的發(fā)展。目的:篩選GBM病人預(yù)后相關(guān)的基因,發(fā)現(xiàn)長生存期GBM患者的臨床特點及腫瘤分子表達(dá)特征。提高對GBM患者的治療效果,為預(yù)后評估提供依據(jù)。方法:首先,應(yīng)用WebArrayDB對微陣列數(shù)據(jù)進(jìn)行整合分析,我們篩選GEO數(shù)據(jù)庫中GBM長生存期患者(LTSs)和短生存期患者(STSs)相關(guān)性最大的前100個基因,再同TCGA和REMBRANDT數(shù)據(jù)庫的提供的候選基因進(jìn)行對比分析,最終篩選出可評估患者預(yù)后的 3 個基因:Fibulin-4,IGFBP-2 和 CHI3L1。然后應(yīng)用收集的77例GBM患者的石蠟包埋組織(FFPE)樣本,提取DNA和RNA,應(yīng)用甲基化特異性定量PCR技術(shù)(qMSP)檢測腫瘤MGMT啟動子甲基化狀態(tài),用實時熒光定量PCR(qPCR)來檢測腫瘤中上述基因的表達(dá)。研究基因與患者預(yù)后相關(guān)性,為GBM預(yù)后的評估提供依據(jù)。結(jié)果:應(yīng)用WebArrayDB對GEO數(shù)據(jù)庫微陣列數(shù)據(jù)的整合分析,發(fā)現(xiàn)Fibulin-4,IGFBP-2和CHI3L1 3個基因與GBM患者的預(yù)后相關(guān)。在我們的實驗中,LTS組MGMT啟動子甲基化發(fā)生率為73.3%(11/15),STS組MGMT啟動子甲基化發(fā)生率為38.7%(24/62)。兩組之間有顯著差異(p0.01)。GBM樣本中3個基因的mRNA表達(dá)水平明顯高于正常腦組織中(p0.01),且LTS組樣本3個基因的表達(dá)水平明顯低于STS組(p0.01),多因素分析顯示Fibulin-4和IGFBP-2的表達(dá)與病人預(yù)后的相關(guān)性顯著(P0.05)。Kaplan-Meier分析顯示Fibulin-4和IGFBP-2和病人生存期密切相關(guān)(Fibulin-4 p0.01;IGFBP-2 p0.05)。結(jié)論:Fibulin-4和IGFBP2同GBM病人的預(yù)后密切相關(guān),其表達(dá)情況可以作為評估患者預(yù)后的依據(jù)。
[Abstract]:Background: one of the most common and most malignant brain tumors in the adult central nervous system (CNS) is:: GBM, despite the use of standard treatments, including surgical resection, postoperative radiotherapy, and temozolidomide chemotherapy. But the prognosis of most patients is still poor. A small number of patients have a relatively good prognosis. The median survival time was 24 months or longer. The study found that the sensitivity and prognosis of patients with GBM were influenced by many molecular markers. Finding the factors related to the prognosis of GBM patients could improve the survival rate of the patients. Significant. Bioinformation technology allows for homology analysis of large amounts of microarray data in databases, Similarity analysis and so on make us study gene regulation at the whole gene level. Therefore, the application of bioinformatics has greatly promoted the development of basic medical research. The clinical features and tumor molecular expression of GBM patients with long survival period were found. The therapeutic effect of GBM patients was improved and the basis for prognosis evaluation was provided. Methods: firstly, microarray data were integrated and analyzed by WebArrayDB. We screened the top 100 genes with the greatest correlation between GBM long survival patients and short survival patients in GEO databases, and compared them with the candidate genes provided by TCGA and REMBRANDT databases. Finally, three genes, 1: Fibulin-4 IGFBP-2 and CHI3L1, were selected to evaluate the prognosis of patients. The paraffin embedded tissue samples of 77 patients with GBM were collected. DNA and RNAs were extracted, methylation-specific quantitative PCR technique was used to detect the methylation status of tumor MGMT promoter, and real-time fluorescence quantitative PCR was used to detect the expression of these genes. Results: WebArrayDB was used to analyze the microarray data of GEO database. In our experiment, the incidence of methylation of MGMT promoter was 73.33% and the incidence of methylation of MGMT promoter in MGMT group was 38.7% 24% 62%. There was a significant difference between the two groups (p0.01. GBM). The expression level of three genes in LTS group was significantly lower than that in STS group. Multivariate analysis showed that the expression of Fibulin-4 and IGFBP-2 was significantly correlated with the prognosis of patients. Kaplan-Meier analysis showed that Fibulin-4 and IGFBP-2 were significantly correlated with the prognosis of patients. Fibulin-4 p0.01 IGFBP-2 p0.05. Conclusion the prognosis of patients with GBM is closely related to the prognosis of patients with GBM. Its expression can be used as a basis for evaluating the prognosis of patients.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R739.4

【參考文獻(xiàn)】

相關(guān)期刊論文 前4條

1 張琳;瞿愛東;;胰島素樣生長因子家族與相關(guān)疾病[J];國際生物制品學(xué)雜志;2016年06期

2 熊筱晶;;GEO基因表達(dá)數(shù)據(jù)庫中芯片技術(shù)平臺的統(tǒng)計分析[J];生命的化學(xué);2009年01期

3 周開甲;李守巍;江濤;;IGFBP-2在高級別腦膠質(zhì)瘤中作用的研究進(jìn)展[J];中國微侵襲神經(jīng)外科雜志;2007年06期

4 許振亮;劉則淵;葛莉;趙玉鵬;;基于知識圖譜的國際生物科學(xué)與工程前沿計量研究[J];情報學(xué)報;2009年02期

，

本文編號：1548804