本文選題：膠質(zhì)瘤 + 維吾爾族　； 參考：《新疆醫(yī)科大學(xué)》2014年博士論文

【摘要】：目的：總結(jié)新疆地區(qū)維、漢族膠質(zhì)瘤患者的臨床特點(diǎn)，分析相關(guān)臨床因素的分布特點(diǎn)，結(jié)合隨訪資料，進(jìn)行生存分析。通過(guò)對(duì)P53、MGMT、PTEN蛋白及Ki-67在膠質(zhì)瘤中表達(dá)及其與膠質(zhì)瘤臨床特征的關(guān)系，探討膠質(zhì)瘤相關(guān)分子標(biāo)記如P53、MGMT、PTEN、Ki-67蛋白在新疆維、漢族膠質(zhì)瘤患者間的表達(dá)差異及其與膠質(zhì)瘤發(fā)生、發(fā)展中的關(guān)系。首次進(jìn)行新疆維、漢族患者膠質(zhì)母細(xì)胞瘤的mRNA基因表達(dá)譜及全基因組甲基化表達(dá)譜差異檢測(cè)，篩選并初步探討差異表達(dá)的相關(guān)基因在新疆維、漢族患者膠質(zhì)母細(xì)胞瘤的發(fā)病機(jī)制及預(yù)后轉(zhuǎn)歸中的意義。方法：1）收集新疆醫(yī)科大學(xué)附屬腫瘤醫(yī)院及新疆醫(yī)科大學(xué)第一附屬醫(yī)院神經(jīng)外科自建院以來(lái)經(jīng)治的成人腦膠質(zhì)瘤患者共985例，其中維吾爾族、漢族膠質(zhì)瘤患者共有843例，其他民族如哈薩克族、回族、蒙古族等共有142例。收集并整理842例膠質(zhì)瘤患者的一般資料、臨床表現(xiàn)、影像學(xué)特征、臨床病理學(xué)特點(diǎn)等信息，初步比較維、漢族膠質(zhì)瘤患者在發(fā)病和臨床特點(diǎn)分布情況，進(jìn)行統(tǒng)計(jì)學(xué)分析。選取2010年1月～2013年5月新疆醫(yī)科大學(xué)附屬腫瘤醫(yī)院的111例膠質(zhì)瘤患者進(jìn)行回顧性電話隨訪及復(fù)診隨訪，其中維吾爾族、漢族患者共有80例，其他民族共有31例。運(yùn)用免疫組織化學(xué)SP法分別檢測(cè)隨訪資料完整的80例膠質(zhì)瘤組織的P53、MGMT、PTEN蛋白及Ki-67的表達(dá)情況；比較維、漢族膠質(zhì)瘤中P53、MGMT、PTEN、Ki-67的表達(dá)差異以及P53、MGMT、PTEN、Ki-67蛋白表達(dá)與膠質(zhì)瘤患者臨床特征的關(guān)系；2）運(yùn)用Illumina HT-12mRNA表達(dá)譜芯片檢測(cè)6例膠質(zhì)母細(xì)胞瘤（其中維、漢族各3例）組織中的基因表達(dá)情況，初步篩選維、漢族膠質(zhì)母細(xì)胞瘤中存在的相同基因及差異表達(dá)基因。通過(guò)提取組織總RNA，反轉(zhuǎn)錄成cDNA，將標(biāo)記的cDNA與基因表達(dá)譜芯片雜交，最后讀取數(shù)據(jù)及獲得圖像，進(jìn)行生物功能信息學(xué)分析。所有檢測(cè)樣品均通過(guò)6類內(nèi)參質(zhì)控檢測(cè)；運(yùn)用免疫組織化學(xué)SP法檢測(cè)膠質(zhì)母細(xì)胞瘤相關(guān)分子標(biāo)記物，與篩選出來(lái)的表達(dá)譜差異表達(dá)基因進(jìn)行綜合分析和驗(yàn)證；3）運(yùn)用Illumina Methylation450K全基因組甲基化芯片檢測(cè)6例膠質(zhì)母細(xì)胞瘤（其中維、漢族各3例）組織中的甲基化表達(dá)情況，初步篩選維、漢族膠質(zhì)母細(xì)胞瘤中差異表達(dá)的甲基化位點(diǎn)及其對(duì)應(yīng)的相關(guān)基因。通過(guò)提取組織DNA，經(jīng)過(guò)亞硫酸鹽處理，與甲基化芯片雜交，讀取數(shù)據(jù)及獲得圖像，進(jìn)行生物功能信息學(xué)分析。所有樣品均通過(guò)11類內(nèi)參質(zhì)控檢測(cè)；對(duì)維、漢族膠質(zhì)母細(xì)胞瘤中篩選出來(lái)的差異甲基化位點(diǎn)對(duì)應(yīng)的差異基因，與mRNA表達(dá)譜芯片篩選的差異基因的結(jié)果分別進(jìn)行高甲基化且基因低表達(dá)及低甲基化且基因高表達(dá)的聯(lián)合分析，篩選新疆維、漢族膠質(zhì)母細(xì)胞瘤中可能存在的關(guān)鍵差異基因。結(jié)果：1）在所有入組842例膠質(zhì)瘤病例中，男性481例，女性362例，年齡1～79歲，平均年齡40.14±18.03歲，其中維族342例，漢族501例。維、漢族膠質(zhì)瘤患者在不同WHO組織學(xué)分級(jí)的分布差異有統(tǒng)計(jì)學(xué)意義（P＜0.05）。所選病例的組織學(xué)類型中，星形細(xì)胞瘤（含膠質(zhì)母細(xì)胞瘤）的例數(shù)最多達(dá)554例（554/842，65.72%）；室管膜腫瘤共149例（149/842，17.67%）；少突膠質(zhì)細(xì)胞腫瘤共50例（50/842，5.93%）；少突星形細(xì)胞腫瘤共12例（12/842，1.42%）；脈絡(luò)叢腫瘤共7例（7/842，0.83％）；神經(jīng)元混合性神經(jīng)元-膠質(zhì)瘤共11例（11/842，1.30%）；胚胎性腫瘤共54例（54/842，6.41％）；松果體腫瘤共6例（6/842，0.71%）。80例隨訪資料完整的膠質(zhì)瘤病例中。膠質(zhì)瘤患者中民族（P=0.000）、腫瘤病理分級(jí)（P=0.000）、是否行放、化療（P=0.009）和腫瘤是否全切（P=0.003）這四項(xiàng)指標(biāo)可能是影響患者預(yù)后的獨(dú)立危險(xiǎn)因素。P53、MGMT、PTEN蛋白和Ki-67的陽(yáng)性率分別為66.25%（53/80）、65%（52/80）、45%（36/80）和47.5%（38/80）。維、漢族膠質(zhì)瘤患者中MGMT、P53蛋白和Ki-67表達(dá)在不同WHO組織學(xué)分級(jí)組中的差異有統(tǒng)計(jì)學(xué)意義（P＜0.05），而在不同年齡、性別、民族及腫瘤部位、病灶大小、侵犯臨近腦葉情況等各組中的差異均無(wú)統(tǒng)計(jì)學(xué)意義（P＞0.05）；PTEN蛋白表達(dá)在不同腫瘤部位及WHO組織學(xué)分級(jí)組中的差異有統(tǒng)計(jì)學(xué)差異（P＜0.05），而在不同年齡、性別、民族、病灶大小、是否侵犯臨近腦葉情況等各組中的差異均無(wú)統(tǒng)計(jì)學(xué)意義（P＞0.05）。2）將芯片雜交掃描圖片導(dǎo)入IlluminaGenomeStudio軟件，得到校正后的數(shù)據(jù)，利用R語(yǔ)言lumi包進(jìn)行標(biāo)準(zhǔn)化處理及差異基因篩選（P＜0.05）；利用Web Gestalt軟件，對(duì)差異基因進(jìn)行GO和KEGG分析（P＜0.05），維、漢族患者膠質(zhì)母細(xì)胞瘤mRNA表達(dá)譜的比較分析發(fā)現(xiàn)，篩選出顯著差異表達(dá)的基因共有1475個(gè)，其中表達(dá)上調(diào)的基因有669個(gè)（44.84％），表達(dá)下調(diào)的基因有807個(gè)（55.16％）（其中有1個(gè)基因（STRC）對(duì)應(yīng)2個(gè)轉(zhuǎn)錄本，1個(gè)轉(zhuǎn)錄本表達(dá)上調(diào)1個(gè)轉(zhuǎn)錄本表達(dá)下調(diào)），差異基因主要參與了代謝過(guò)程、生物調(diào)節(jié)、對(duì)刺激反應(yīng)、多細(xì)胞的有機(jī)過(guò)程等，其中包含小GTP酶調(diào)節(jié)信號(hào)通路、Ras信號(hào)通路、神經(jīng)元反應(yīng)蛋白調(diào)節(jié)、中樞神經(jīng)系統(tǒng)髓鞘形成等多個(gè)功能節(jié)點(diǎn)；同時(shí)也參與了多條與腫瘤發(fā)生相關(guān)的信號(hào)通路，如：代謝通路、癌通路、MAPK信號(hào)通路、TGF-β信號(hào)通路、神經(jīng)營(yíng)養(yǎng)因子信號(hào)轉(zhuǎn)導(dǎo)通路、mTOR信號(hào)通路等。3）將芯片雜交掃描圖片導(dǎo)入Illumina GenomeStudio軟件，得到校正后的數(shù)據(jù)，使用controls標(biāo)準(zhǔn)化；通過(guò)IlluminaCustom進(jìn)行差異位點(diǎn)篩選，結(jié)果經(jīng)過(guò)多重檢驗(yàn)校正和篩選條件為，篩選條件為|DiffScore|≥13|DeltaBeta|≥0.2；利用WebGestalt軟件，對(duì)差異甲基化位點(diǎn)對(duì)應(yīng)的基因進(jìn)行GO和KEGG的功能注釋（P＜0.05），維、漢族患者膠質(zhì)母細(xì)胞瘤全基因組甲基化表達(dá)譜的比較分析發(fā)現(xiàn)，篩選出顯著差異表達(dá)的6406個(gè)差異位點(diǎn)所對(duì)應(yīng)的1903個(gè)基因中，表達(dá)上調(diào)的位點(diǎn)有1953個(gè)（1953/6406，30.49％），表達(dá)下調(diào)的位點(diǎn)有4453個(gè)（4453/6406，69.51％），這些差異位點(diǎn)對(duì)應(yīng)的相關(guān)基因主要參與了生物調(diào)節(jié)、代謝過(guò)程、多細(xì)胞的有機(jī)過(guò)程、對(duì)刺激反應(yīng)、發(fā)育過(guò)程等，其中包含小GTP酶調(diào)節(jié)信號(hào)通路、Ras信號(hào)通路、神經(jīng)元反應(yīng)蛋白調(diào)節(jié)、中樞神經(jīng)系統(tǒng)髓鞘形成等多個(gè)功能節(jié)點(diǎn)；同時(shí)也參與了多條與腫瘤發(fā)生相關(guān)的信號(hào)通路，如：神經(jīng)分化、神經(jīng)發(fā)育、MAPK信號(hào)通路、TGF-β信號(hào)通路、神經(jīng)營(yíng)養(yǎng)因子信號(hào)轉(zhuǎn)導(dǎo)通路、mTOR信號(hào)通路等。4）通過(guò)對(duì)維、漢族膠質(zhì)母細(xì)胞瘤mRNA基因表達(dá)譜及其全基因組甲基化狀態(tài)的關(guān)聯(lián)性分析，初步通過(guò)對(duì)差異表達(dá)基因及差異甲基化位點(diǎn)所對(duì)應(yīng)的差異基因表達(dá)上調(diào)、下調(diào)關(guān)系進(jìn)行比對(duì)發(fā)現(xiàn)，維、漢族膠質(zhì)母細(xì)胞瘤中全基因組甲基化芯片篩選的高甲基化位點(diǎn)（表達(dá)上調(diào)）對(duì)應(yīng)的基因中與表達(dá)譜篩選的差異基因中低表達(dá)（表達(dá)下調(diào)）的基因共同的有12個(gè)，分別是ADARB2，ATP11C，ATPGD1，C1orf59，GPR62，PIK3C2B，PIR，PLLP，SLC5A11，ZFYVE27，ZNF415，ZNF536；而維、漢族膠質(zhì)母細(xì)胞瘤全基因組甲基化芯片篩選的低甲基化位點(diǎn)（表達(dá)下調(diào)）對(duì)應(yīng)的基因中與表達(dá)譜篩選的差異基因中高表達(dá)（表達(dá)上調(diào)）的基因共同的有4個(gè)，分別是HSD17B10，MRPL3，ZBTB5，ZNF662。結(jié)論：1）與新疆地區(qū)漢族膠質(zhì)瘤患者相比，維族膠質(zhì)瘤患者有發(fā)病年齡輕、男性比例高、低級(jí)別膠質(zhì)瘤比例較高、星形細(xì)胞瘤比例高的趨勢(shì)。膠質(zhì)瘤患者臨床特點(diǎn)中的民族、腫瘤病理分級(jí)、是否行放、化療和腫瘤是否全切等指標(biāo)可能是影響膠質(zhì)瘤患者預(yù)后轉(zhuǎn)歸的因素。聯(lián)合檢測(cè)MGMT、P53、PTEN蛋白和Ki-67在膠質(zhì)瘤中的表達(dá)可以作為判定膠質(zhì)瘤生物學(xué)行為和預(yù)后的參考指標(biāo)。2）新疆維、漢族患者膠質(zhì)母細(xì)胞瘤mRNA表達(dá)譜芯片和全基因組甲基化芯片篩查出的眾多相同基因及相同甲基化位點(diǎn)，也篩選出不同民族間的差異表達(dá)基因及差異甲基化位點(diǎn)。這些差異基因主要參與了代謝過(guò)程、生物調(diào)節(jié)、對(duì)刺激反應(yīng)、多細(xì)胞的有機(jī)過(guò)程、發(fā)育過(guò)程等，其中包含小GTP酶調(diào)節(jié)信號(hào)通路、Ras信號(hào)通路、神經(jīng)元反應(yīng)蛋白調(diào)節(jié)、中樞神經(jīng)系統(tǒng)髓鞘形成等多個(gè)功能節(jié)點(diǎn)；同時(shí)也參與了多條與腫瘤發(fā)生相關(guān)的信號(hào)通路，如：代謝通路、癌通路、神經(jīng)分化、神經(jīng)發(fā)育、MAPK信號(hào)通路、TGF-β信號(hào)通路、神經(jīng)營(yíng)養(yǎng)因子信號(hào)轉(zhuǎn)導(dǎo)通路、mTOR信號(hào)通路等。3）mRNA表達(dá)譜及甲基化狀態(tài)的關(guān)聯(lián)性分析提示維、漢族膠質(zhì)母細(xì)胞瘤全基因組甲基化芯片篩選的高甲基化位點(diǎn)（表達(dá)上調(diào)）對(duì)應(yīng)的基因中與mRNA表達(dá)譜篩選的差異基因中低表達(dá)（表達(dá)下調(diào)）的基因共同的有12個(gè)，分別是ADARB2，ATP11C，ATPGD1，C1orf59，GPR62，PIK3C2B，PIR，PLLP，SLC5A11，ZFYVE27，ZNF415，ZNF536；而維、漢族膠質(zhì)母細(xì)胞瘤全基因組甲基化芯片篩選的低甲基化位點(diǎn)（表達(dá)下調(diào)）對(duì)應(yīng)的基因中與mRNA表達(dá)譜篩選的差異基因中高表達(dá)（表達(dá)上調(diào)）的基因共同的有4個(gè)，分別是HSD17B10，MRPL3，ZBTB5，ZNF662。對(duì)這些基因的進(jìn)一步研究有助于在基因?qū)用嫔辖沂拘陆貐^(qū)維、漢族膠質(zhì)瘤患者發(fā)病機(jī)制、預(yù)后轉(zhuǎn)歸等方面可能存在的差異，，也為將來(lái)的進(jìn)一步在分子水平上對(duì)新疆膠質(zhì)瘤患者的的研究和靶向治療提供新的依據(jù)。
[Abstract]:Objective: To summarize the clinical characteristics of the patients with human glioma in Xinjiang, to analyze the distribution characteristics of the related clinical factors and to analyze the survival analysis with the follow-up data. The expression of P53, MGMT, PTEN protein and Ki-67 in glioma and the relationship between the glioma and the clinical characteristics of glioma are discussed, and the molecular markers of glioma, such as P53, MGMT, PTEN, Ki-67, are discussed. The expression of protein in Xinjiang Wei and Han glioma patients and their relationship with the development of glioma and glioma. The mRNA gene expression profiles and total genome methylation expression profiles of glioblastoma in Xinjiang and Han patients were detected for the first time, and the genes related to differential expression in Xinjiang dimension and Han patients were screened and preliminarily discussed. The significance of the pathogenesis and prognosis of the mass blastoma. Methods: 1) 985 cases of adult brain glioma were collected from the Affiliated Tumor Hospital of Xinjiang Medical University and the First Affiliated Hospital of Xinjiang Medical University since the establishment of the hospital. There were 843 cases of Uygur and Han Chinese gelatoma, and other ethnic groups such as Kazakh. There were 142 cases of ethnic, Hui, Mongolian, etc. collected and collate 842 cases of glioma patients general information, clinical manifestations, imaging features, clinicopathological features and other information, preliminary comparative dimension, Han glioma patients in the incidence and clinical characteristics of the distribution, statistical analysis, selected from January 2010 to May 2013 affiliated to the Xinjiang Medical University affiliated. 111 patients with glioma in the cancer hospital were followed up with retrospective telephone follow-up and follow-up visit. There were 80 cases in Uygur and Han people and 31 in other nationalities. The expression of P53, MGMT, PTEN protein and Ki-67 in 80 glioma tissues were detected by immunohistochemical SP method. The expression of P53, MGMT, PTEN, Ki-67 and the relationship between the expression of P53, MGMT, PTEN, Ki-67 protein and the clinical characteristics of the patients with glioma; 2) the detection of the gene expression in the tissues of 6 cases of glioblastoma (among which 3 cases of Han nationality) was detected by Illumina HT-12mRNA expression chip, and the primary screening of the presence of the human glioblastoma in the Han nationality The same gene and differentially expressed genes were extracted by extracting the total tissue RNA and reverse transcriptional into cDNA. The labeled cDNA was hybridized with the gene expression chip. Finally, the data were read and the image was obtained, and the bioinformatics analysis was performed. All the samples were detected by 6 kinds of internal parameters, and the immunohistochemical SP method was used to detect the glioblastoma correlation. Molecular markers, integrated analysis and verification with the differentially expressed genes expressed by the screened expression profiles, and 3) detection of methylation in 6 cases of glioblastoma (including 3 of the Han people) by Illumina Methylation450K genome methylation chip, and preliminary screening of the differential expression in the human glioblastoma of the Han nationality. By extracting tissue DNA, using sulfite treatment, hybridization with methylation chips, reading data and obtaining images, bioinformatics analysis. All samples were detected by 11 types of internal parameters, and the differential methylation sites were screened in the Uygur and Han glioblastoma. The difference genes, respectively, were methylation, low gene expression, low methylation and high expression of genes, and the key differentially differentially expressed genes in Xinjiang and Han glioblastoma were screened by the results of differential genes screened by mRNA expression chip. Results: 1) in all 842 cases of glioma, 481 cases were male. There were 362 cases of female, aged 1~79 years, with an average age of 40.14 + 18.03 years old, including 342 cases of Uygur and 501 cases of Han nationality. There were significant differences in the distribution of WHO histology among the patients with glioma in the Han nationality (P < 0.05). The number of astrocytomas (including glioblastoma) was up to 554 cases (554/842,65.72%) in the histological type of the selected cases. 149 cases of ependyma tumor (149/842,17.67%); 50 cases of oligodendrocyte tumor (50/842,5.93%); 12 cases of oligodendroid astrocytoma (12/842,1.42%); 7 cases of choroid plexus tumor (7/842,0.83%); 11 cases of neuron mixed neuron glioma (11/ 842,1.30%); 54 cases of embryonal tumor (54/842,6.41%); pineal body, and pineal body. In a total of 6 cases (6/842,0.71%), a total of.80 cases were followed up with a complete follow-up of glioma cases. The four indexes of the group (P=0.000), tumor pathological grading (P=0.000), chemotherapy (P=0.009) and tumor total resection (P=0.003) may be the independent risk factors that affect the prognosis of the patients:.P53, MGMT, PTEN protein and Ki-67. The differences in MGMT, P53 and Ki-67 expressions in 66.25% (53/80), 65% (52/80), 45% (36/80) and 47.5% (38/80), and 47.5% (38/80). Human glioma were statistically significant (P < 0.05) in different WHO histology groups (P < 0.05). Study significance (P > 0.05); the difference of PTEN protein expression in different tumor sites and WHO histological grading groups was statistically significant (P < 0.05), and there was no statistical significance (P > 0.05).2) at different ages, sex, nationality, size of the focus, and the invasion of the adjacent lobes (P > 0.05).2). GenomeStudio software, obtained the corrected data, using the R language Lumi package for standardized processing and differential gene screening (P < 0.05). Using Web Gestalt software, GO and KEGG analysis (P < 0.05) of the differential genes (P < 0.05), and the comparison of mRNA expression profiles of the glioblastoma of the Han patients were compared and analyzed, and found that the significant differentially expressed genes were screened out. There are 1475 genes, of which 669 (44.84%) are up-regulated genes, and 807 (55.16%) down regulated genes (of which 1 genes (STRC) correspond to 2 transcripts, 1 transcripts are up regulated by 1 transcriptional downregulation), and the differential genes are mainly involved in metabolic processes, biological regulation, stimulus response, and multicellular organic processes. Several functional nodes, including small GTP enzyme regulation signaling pathway, Ras signaling pathway, neuron reactive protein regulation, central nervous system myelin formation, are also involved in a number of signaling pathways associated with tumor occurrence, such as metabolic pathways, cancer pathways, MAPK signaling pathways, TGF- beta signaling pathways, neurotrophic factor signal transduction pathways, mTOR .3 (signal path, etc.) introduced the chip hybrid scanning picture into Illumina GenomeStudio software, obtained the corrected data, used controls standardization, and screened the difference sites through IlluminaCustom, and the results were corrected by multiple tests and screening conditions, and the screening conditions were DiffScore| > 13|DeltaBeta| > 0.2; WebGestalt software was used. The functional annotation of GO and KEGG (P < 0.05) for the genes corresponding to the differential methylation sites, and the comparative analysis of the total genome methylation profiles of the glioblastoma in Han patients, found that of the 1903 genes corresponding to the 6406 differentially expressed differentially expressed heterotopic points, 1953 (1953/6406,30.49%) were expressed in the up regulated loci. There are 4453 down-regulated sites (4453/6406,69.51%). The related genes are involved in biological regulation, metabolic processes, multicellular organic processes, stimulation responses, development processes, including small GTP enzyme regulation signaling pathway, Ras signaling pathway, neuron reactive protein regulation, and central nervous system myelin shape There are multiple functional nodes, and they also participate in a number of signal pathways related to the occurrence of tumor, such as nerve differentiation, nerve development, MAPK signaling pathway, TGF- beta signaling pathway, neurotrophic factor signal transduction pathway, mTOR signaling pathway and other.4) through the mRNA gene expression profiles and full genome methylation of the Hans and grocin blastoma The correlation analysis of the state, the difference of the high methylation site (expression profile) selected by the whole genome methylation chip in the human glioblastoma of the Han nationality by comparing the up regulation and down regulation of differentially expressed genes and differential methylation sites. ADARB2, ATP11C, ATPGD1, C1orf59, GPR62, PIK3C2B, PIR, PIK3C2B, PIR, PLLP, SLC5A11, ZFYVE27, ZNF415, ZNF536; and the differential genes of the low methylation site (down expression) of the whole genome of the Han glioblastoma selected by the whole genome of the human glioblastoma There are 4 common genes of high expression (up expression), which are HSD17B10, MRPL3, ZBTB5, ZNF662. conclusion: 1) compared with the patients of Xinjiang Han glioma, Uygur glioma patients have a high incidence of age, high male proportion, high ratio of low grade glioma, high proportion of astrocytoma, and the clinical characteristics of glioma patients. A combination of MGMT, P53, PTEN protein and Ki-67 in glioma can be used as a reference index to determine the biological behavior and prognosis of glioma,.2) in Xinjiang and Han patients, and the human glioblastoma in Han patients. Many of the same genes and methylation sites screened by mRNA and all genome methylation chips have also been screened for differentially expressed genes and differential methylation sites among different ethnic groups. These differentially expressed genes are mainly involved in metabolic processes, biological regulation, response to stimulation, multicellular organic processes, and development processes. A number of functional nodes including small GTP enzyme regulation signaling pathway, Ras signaling pathway, neuron reactive protein regulation, central nervous system myelin formation, and a number of signaling pathways associated with tumor occurrence, such as metabolic pathways, cancer pathways, neural differentiation, neurodevelopment, MAPK signaling pathways, TGF- beta signaling pathways, neurotrophic factors Subsignal transduction pathway, mTOR signaling pathway and other.3) mRNA expression profiles and methylation status correlation analysis suggested that the high methylation site (up expression) selected by the whole genome methylation chip of the Hans glioblastoma (up-regulated) corresponding genes with low expression of low expression (down expression) in the differential gene of mRNA expression profiles are 12 ADARB2, ATP11C, ATPGD1, ATPGD1, C1orf59, GPR62, PIK3C2B, PIR, PLLP, SLC5A11, ZFYVE27, ZNF415, ZNF536; and dimension, the low methylation site (down expression) of the whole genome methylation chip screened by the whole genome of the Han nationality glioblastoma (down regulation) of the corresponding genes with high expression (up-regulated expression) in the differential gene screened from the spectrum The further study of these genes, HSD17B10, MRPL3, ZBTB5, and ZNF662., will help to reveal the possible differences in the pathogenesis, prognosis and other aspects of the Xinjiang regional dimension, the prognosis and the prognosis of the Han glioma patients at the gene level, as well as to provide further research and targeted therapy for the patients of Xinjiang glioma at the molecular level. A new basis.
【學(xué)位授予單位】：新疆醫(yī)科大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類號(hào)】：R739.41

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 夏海成;朱正權(quán);劉亮;田海龍;孫哲;;新疆維族和漢族膠質(zhì)瘤患者M(jìn)GMT表達(dá)水平分析并94例報(bào)告[J];中國(guó)神經(jīng)腫瘤雜志;2011年01期

2 仇志坤;沈冬;賽克;陳銀生;馮冰虹;陳忠平;;膠質(zhì)瘤干細(xì)胞樣細(xì)胞中MGMT表達(dá)以及與替莫唑胺的耐藥關(guān)系研究[J];中國(guó)神經(jīng)腫瘤雜志;2011年02期

3 趙軍;王宏偉;宋繼偉;肖建奇;曲藝;張軍;歐陽(yáng)海峰;盛學(xué)東;谷樹清;于雷;于廣久;;PTEN基因?qū)δz質(zhì)瘤細(xì)胞增殖及侵襲性影響的體外研究[J];第三軍醫(yī)大學(xué)學(xué)報(bào);2012年06期

4 Zhi-Kun Qiu;Dong Shen;Yin-Sheng Chen;Qun-Ying Yang;Cheng-Cheng Guo;Bing-Hong Feng;Zhong-Ping Chen;;Enhanced MGMT expression contributes to temozolomide resistance in glioma stem-like cells[J];Chinese Journal of Cancer;2014年02期

5 王惠麗;苑召虎;陳志江;姚芳;胡子有;吳炳義;;槲皮素誘導(dǎo)U87細(xì)胞凋亡及對(duì)MDM2-p53負(fù)反饋調(diào)節(jié)的影響[J];南方醫(yī)科大學(xué)學(xué)報(bào);2014年05期

6 陶林;賈薇;楊安強(qiáng);胡文浩;梁偉華;齊翠花;孫琦;井明霞;李鋒;潘曉琳;;普查方法的聯(lián)合應(yīng)用與新疆喀什地區(qū)維族婦女子宮頸癌的調(diào)查分析[J];臨床與實(shí)驗(yàn)病理學(xué)雜志;2010年04期

7 周福安;古麗那爾·阿布拉江;張志明;張巍;;PI3K/AKT/mTOR信號(hào)轉(zhuǎn)導(dǎo)通路相關(guān)蛋白在腦膠質(zhì)瘤中的表達(dá)及臨床意義[J];臨床神經(jīng)病學(xué)雜志;2012年04期

8 蔡國(guó)恩;陸欽池;;基因芯片在癲癇研究中的應(yīng)用進(jìn)展[J];上海交通大學(xué)學(xué)報(bào)(醫(yī)學(xué)版);2007年11期

9 薛偉明;王占祥;馬永會(huì);鐘山;陳佩瓊;譚國(guó)偉;葉永造;;EGFL7和PTEN在人腦膠質(zhì)瘤中的表達(dá)[J];中華神經(jīng)外科疾病研究雜志;2011年06期

10 谷化平;尚培中;;EGFR、VEGF和PTEN在結(jié)直腸癌中表達(dá)及與其臨床病理特征的關(guān)系[J];實(shí)用癌癥雜志;2011年03期

相關(guān)博士學(xué)位論文 前1條

1 王亮;耐藥性癲癇分子病理機(jī)制及生物標(biāo)記物相關(guān)研究[D];重慶醫(yī)科大學(xué);2011年

本文編號(hào)：1899481