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学科主题: 基础医学
题名:
Layered Signaling Regulatory Networks Analysis of Gene Expression Involved in Malignant Tumorigenesis of Non-Resolving Ulcerative Colitis via Integration of Cross-Study Microarray Profiles
作者: Fan, Shengjun1,2; Pan, Zhenyu3; Geng, Qiang4; Li, Xin1,2; Wang, Yefan1,2; An, Yu1,2; Xu, Yan5; Tie, Lu1,2; Pan, Yan1,2; Li, Xuejun1,2
刊名: PLOS ONE
发表日期: 2013-06-25
DOI: 10.1371/journal.pone.0067142
卷: 8, 期:6
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Multidisciplinary Sciences
研究领域[WOS]: Science & Technology - Other Topics
关键词[WOS]: EPIDERMAL-GROWTH-FACTOR ; CD4(+) T-CELLS ; INFLAMMATORY-BOWEL-DISEASE ; COLORECTAL-CANCER ; BREAST-CANCER ; BIOLOGICAL NETWORKS ; B-CELLS ; RECOMBINANT ERYTHROPOIETIN ; HEPATOCELLULAR-CARCINOMA ; TRANSCRIPTION FACTORS
英文摘要:

Background: Ulcerative colitis (UC) was the most frequently diagnosed inflammatory bowel disease (IBD) and closely linked to colorectal carcinogenesis. By far, the underlying mechanisms associated with the disease are still unclear. With the increasing accumulation of microarray gene expression profiles, it is profitable to gain a systematic perspective based on gene regulatory networks to better elucidate the roles of genes associated with disorders. However, a major challenge for microarray data analysis is the integration of multiple-studies generated by different groups.

Methodology/Principal Findings: In this study, firstly, we modeled a signaling regulatory network associated with colorectal cancer (CRC) initiation via integration of cross-study microarray expression data sets using Empirical Bayes (EB) algorithm. Secondly, a manually curated human cancer signaling map was established via comprehensive retrieval of the publicly available repositories. Finally, the co-differently-expressed genes were manually curated to portray the layered signaling regulatory networks.

Results: Overall, the remodeled signaling regulatory networks were separated into four major layers including extracellular, membrane, cytoplasm and nucleus, which led to the identification of five core biological processes and four signaling pathways associated with colorectal carcinogenesis. As a result, our biological interpretation highlighted the importance of EGF/EGFR signaling pathway, EPO signaling pathway, T cell signal transduction and members of the BCR signaling pathway, which were responsible for the malignant transition of CRC from the benign UC to the aggressive one.

Conclusions: The present study illustrated a standardized normalization approach for cross-study microarray expression data sets. Our model for signaling networks construction was based on the experimentally-supported interaction and microarray co-expression modeling. Pathway-based signaling regulatory networks analysis sketched a directive insight into colorectal carcinogenesis, which was of significant importance to monitor disease progression and improve therapeutic interventions.

语种: 英语
所属项目编号: 91129727 ; 81020108031 ; 30973558 ; 81270049 ; B07001
项目资助者: National Natural Science Foundation of China ; Ministry of Education of China
WOS记录号: WOS:000321223000085
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/68021
Appears in Collections:基础医学院_药理学系_期刊论文

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作者单位: 1.Xian Childrens Hosp, Dept Pharm, Xian, Peoples R China
2.Peking Univ, Sch Basic Med Sci, Dept Pharmacol, State Key Lab Nat & Biomimet Drugs, Beijing 100871, Peoples R China
3.Peking Univ, Beijing Key Lab Tumor Syst Biol, Beijing 100871, Peoples R China
4.Peking Univ, Peoples Hosp, Dept Cardiol, Beijing 100871, Peoples R China
5.Shandong Univ, Qilu Childrens Hosp, Pediat Res Inst, Jinan 250100, Peoples R China

Recommended Citation:
Fan, Shengjun,Pan, Zhenyu,Geng, Qiang,et al. Layered Signaling Regulatory Networks Analysis of Gene Expression Involved in Malignant Tumorigenesis of Non-Resolving Ulcerative Colitis via Integration of Cross-Study Microarray Profiles[J]. PLOS ONE,2013,8(6).
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