Systems biology analysis of Sjögren's syndrome and mucosa-associated lymphoid tissue lymphoma in parotid glands.
Systems biology analysis of Sjögren's syndrome and mucosa-associated lymphoid tissue lymphoma in parotid glands.
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DOI：
10.1002/art.24150
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发表时间：
2009-01
影响因子：
--
通讯作者：
Wong, David T.
中科院分区：
文献类型：
--
作者：
Hu, Shen;Zhou, Michael;Jiang, Jiang;Wang, Jianghua;Elashoff, David;Gorr, Sven;Michie, Sara A.;Spijkervet, Fred K. L.;Bootsma, Hendrika;Kallenberg, Cees G. M.;Vissink, Arjan;Horvath, Steve;Wong, David T.
通过对表现为原发性干燥综合征（pSS）和pSS/粘膜相关淋巴组织（pSS/MALT）淋巴瘤表型的腮腺进行系统分析，确定与疾病发病机制相关的关键靶基因和激活的信号通路。采用系统生物学方法分析非pSS、pSS和pSS/MALT淋巴瘤患者的腮腺组织。同时进行表达微阵列分析和蛋白质组学分析，然后进行加权基因共表达网络分析（WGCNA）。与pSS和pSS/MALT淋巴瘤相关的基因共表达模块显著富含已知参与免疫/防御反应、细胞凋亡、细胞信号传导、基因调控和氧化应激的基因。详细的功能途径分析表明，PSS相关模块富含蛋白酶体降解，细胞凋亡，信号肽（MHC）I类，补体激活，细胞生长和死亡，和整合素介导的细胞粘附的基因。pSS/MALT相关模块富含参与翻译、核糖体、蛋白酶降解、I类信号肽（MHC）、G13信号传导途径、补体激活和整合素介导的细胞粘附的基因。基因表达和蛋白质组学数据的组合分析涉及6个高度连接的枢纽基因用于区分pSS与非pSS对照，以及8个枢纽基因用于区分pSS/MALT淋巴瘤与pSS。pSS和pSS/MALT腮腺的系统生物学分析揭示了与疾病发病机制相关的途径和分子靶点。所鉴定的基因模块/通路为pSS和pSS/MALT淋巴瘤的分子机制提供了进一步的见解。所鉴定的疾病中心基因代表了治疗干预、诊断和预后的有希望的靶点。
To identify key target genes and activated signal pathways associated with the disease pathogenesis by conducting a systems analysis of parotid gland manifesting primary Sjögren’s syndrome (pSS) and pSS/mucosa-associated lymphoid tissue (pSS/MALT) lymphoma phenotypes. A systems biologic approach was used to analyze parotid gland tissues obtained from non-pSS, pSS and pSS/MALT lymphoma patients. Concurrent expression microarray profiling and proteomic analysis were performed followed by weighted gene co-expression network analysis (WGCNA). Gene co-expression modules related to pSS and pSS/MALT lymphoma are significantly enriched with genes known to be involved in immune/defense response, apoptosis, cell signaling, gene regulation, and oxidative stress. A detailed functional pathway analysis indicates that the pSS-associated modules are enriched with genes involved in proteasome degradation, apoptosis, signal peptides (MHC) class I, complement activation, cell growth and death, and integrin-mediated cell adhesion. The pSS/MALT-associated modules are enriched with genes involved in translation, ribosome, protease degradation, signal peptides (MHC) class I, G13 signaling pathway, complement activation, and Integrin-mediated cell adhesion. The combined analysis of gene expression and proteomics data implicates six highly connected hub genes for distinguishing pSS from non-pSS controls, and eight hub genes for distinguishing pSS/MALT lymphoma from pSS. Systems biologic analysis of pSS and pSS/MALT parotid glands reveals pathways and molecular targets associated with the disease pathogenesis. The identified gene modules/pathways provide further insights into the molecular mechanisms of pSS and pSS/MALT lymphoma. The identified disease hub genes represent promising targets for therapeutic intervention, diagnosis, and prognosis.
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影响因子：
11.2
作者：
Choi, Kyu Jin;Piao, Yu Ji;Kim, Sung Soo
通讯作者：
Kim, Sung Soo
影响因子：
2.3
作者：
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通讯作者：
Ferraccioli, G
DOI：
10.1073/pnas.0605938103
发表时间：
2006-11-21
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
64.5
作者：
Li, P;Nijhawan, D;Wang, XD
通讯作者：
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DOI：
10.1073/pnas.0605457103
发表时间：
2006-08-22
影响因子：
11.1
作者：
Gargalovic, Peter S.;Imura, Minori;Lusis, Aldons J.
通讯作者：
Lusis, Aldons J.