本文關(guān)鍵詞： HPV 口咽癌 生物信息學(xué) 蛋白質(zhì)交互作用網(wǎng)絡(luò) 聚類(lèi)分析　出處：《浙江大學(xué)》2015年博士論文　論文類(lèi)型：學(xué)位論文

【摘要】：研究背景： 口咽癌(Oropharyngeal Squamous Cell Carcinoma, OPSCC)是頭頸部常見(jiàn)的惡性腫瘤。近年來(lái),人乳頭狀瘤病毒(Human Papilloma Virus, HPV)感染,被認(rèn)為是除吸煙和飲酒外另一個(gè)重要的致病因素。臨床研究發(fā)現(xiàn)感染HPV與未感染HPV的OPSCC患者的臨床特征和預(yù)后不同。國(guó)際癌癥研究機(jī)構(gòu)的研究表明HPV感染的OPSCC患者可進(jìn)一步細(xì)分為HPV激活組和HPV未激活組,前者明顯較后者及HPV陰性口咽癌患者預(yù)后好。HPV在口咽癌的致病機(jī)理仍未被闡明。 研究目的： 分析HPV激活、HPV未激活和HPV陰性三種OPSCC的基因芯片數(shù)據(jù)。結(jié)合基因芯片數(shù)據(jù)和蛋白質(zhì)數(shù)據(jù)庫(kù),構(gòu)建并分析三種OPSCC蛋白質(zhì)-蛋白質(zhì)相互作用(Protein-Protein Interaction, PPI)網(wǎng)絡(luò)。 研究方法： 1、使用R程序的Limma數(shù)據(jù)包將HPV激活、HPV未激活和HPV陰性三種OPSCC與正�？谘式M織的基因芯片數(shù)據(jù)分別進(jìn)行比較,獲取三組的差異性表達(dá)基因(Differentially Expressed Genes, DEGs),并進(jìn)行GO (Gene Ontology)分析和KEGG通路分析。 2、合并HPRD、 MINT、 BioGRID三大蛋白質(zhì)數(shù)據(jù)庫(kù)中的蛋白質(zhì)交互作用(Protein-Protein Interaction, PPI)數(shù)據(jù),制作PPI數(shù)據(jù)庫(kù)。 3、根據(jù)三組DEGs信息,結(jié)合PPI數(shù)據(jù)庫(kù)信息,構(gòu)造三種OPSCC相對(duì)應(yīng)的蛋白質(zhì)交互作用網(wǎng)絡(luò),使用ClusterOne進(jìn)行聚類(lèi)分析。 研究結(jié)果： 1、與正�？谘式M織的基因芯片相比,HPV激活組有184個(gè)基因,HPV未激活組有482個(gè)基因,HPV陰性組有543個(gè)基因存在顯著的差異性表達(dá)。三組DEGs的功能分析提示這些DEGs均集中在“上皮發(fā)育”、“上皮分化”、“細(xì)胞黏附”、“生物黏附”、“胞外基質(zhì)”、“細(xì)胞因子活性”等條目上。 2、三種OPSCC相對(duì)應(yīng)的PPI網(wǎng)絡(luò)被建立。對(duì)其進(jìn)行聚類(lèi)分析后發(fā)現(xiàn),COL1A1是三張網(wǎng)絡(luò)共同的熱點(diǎn)蛋白,UBC及CEACAMs是HPV未激活和HPV陰性O(shè)PSCC的PPI網(wǎng)絡(luò)的熱點(diǎn)蛋白。 研究結(jié)論： 1、上皮發(fā)育分化、細(xì)胞黏附、胞外基質(zhì)改變及細(xì)胞因子紊亂在OPSCC發(fā)生發(fā)展中可能起到重要作用。 2、同HPV激活OPSCC相比,HPV未激活與HPV陰性O(shè)PSCC有更多相似的分子生物學(xué)標(biāo)記物。 3、COL1A1可能是OPSCC的重要生物標(biāo)記物,UBC及CEACAMs可能是HPV未激活和HPV陰性O(shè)PSCC的重要生物標(biāo)記物。
[Abstract]:Background: Oropharyngeal Squamous Cell carcinoma (OPSCC) is a common malignant tumor in head and neck. Human Papilloma virus (HPV) infection. It is considered to be another important pathogenic factor in addition to smoking and drinking. Clinical studies have found that the clinical characteristics and prognosis of OPSCC patients infected with HPV are different from those of OPSCC patients without HPV. The results showed that OPSCC patients infected with HPV could be further subdivided into HPV activated group and HPV inactive group. The prognosis of the former was significantly better than that of the latter and the HPV negative oropharyngeal carcinoma. The pathogenesis of HPVin oropharyngeal carcinoma has not been elucidated. Objectives of the study: To analyze the gene chip data of HPV activated HPV-unactivated and HPV negative OPSCC, combined with gene chip data and protein database. Three OPSCC protein-protein interaction networks were constructed and analyzed. Research methods: 1. Using the Limma data of R program, the HPV activated HPV-unactivated and HPV negative OPSCC were compared with the normal oropharyngeal tissue gene chip data. Three groups of differentially expressed Expressed genes (DEGs) were obtained. Go Gene Ontology) analysis and KEGG pathway analysis were carried out. (2) protein interaction in HPRD, mint, BioGRID protein database was combined with Protein-Protein Interaction. PPI) data, the production of PPI database. 3. According to three groups of DEGs information and PPI database information, three kinds of protein interaction networks corresponding to OPSCC are constructed, and cluster analysis is carried out by ClusterOne. Results of the study: 1. Compared with normal oropharyngeal tissue, there were 184 HPV-activated genes in HPV-activated group and 482 genes in non-HPV-activated group. There were significant differences in the expression of 543 genes in the HPV negative group. The functional analysis of DEGs in the three groups suggested that these DEGs were concentrated in "epithelial development", "epithelial differentiation" and "cell adhesion". "Biological adhesion", "extracellular matrix", "cytokine activity", etc. 2, three PPI networks corresponding to OPSCC were established, and the results of cluster analysis showed that COL1A1 was the common hot protein of the three networks. UBC and CEACAMs are hot spots in PPI network of HPV inactive and HPV negative OPSCC. The study concluded that: 1. Epithelial development and differentiation, cell adhesion, extracellular matrix change and cytokine disorder may play an important role in the development of OPSCC. 2. Compared with HPV activated OPSCC, there were more similar molecular biomarkers between unactivated and HPV negative OPSCC. 3COL1A1 may be an important biomarker of OPSCC and CEACAMs may be an important biomarker of HPV unactivated and HPV negative OPSCC.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2015
【分類(lèi)號(hào)】：R739.85

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