Zhang Xiaoxu, Zhang Yingying, Yu Yanan, Liu Jun, Yuan Ye, Zhao Yijun, Li Haixia, Wang Jie, Wang Zhong
Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China.
J Cell Mol Med. 2015 May;19(5):1094-102. doi: 10.1111/jcmm.12504. Epub 2015 Mar 6.
Diabetes mellitus (DM) and breast cancer (BC) can simultaneously occur in the same patient populations, but the molecular relationship between them remains unknown. In this study, we constructed genetic networks and used modularized analysis approaches to investigate the multi-dimensional characteristics of two diseases and one disease subtype. A text search engine (Agilent Literature Search 2.71) and MCODE software were applied to validate potential subnetworks and to divide the modules, respectively. A total of 793 DM-related genes, 386 type 2 diabetes (T2DM) genes and 873 BC-related genes were identified from the Online Mendelian Inheritance in Man database. For DM and BC, a total of 99 overlapping genes, 9 modules, 29 biological processes and 7 pathways were identified. Meanwhile, for T2DM and BC, 56 overlapping genes, 5 modules, 20 biological processes and 12 pathways were identified. Based on the Gene Ontology functional enrichment analysis of the top 10 non-overlapping modules of the two diseases, 10 biological functions and 5 pathways overlapped between them. The glycosphingolipid and lysosome pathways verified molecular mechanisms of cell death related to both DM and BC. We also identified new biological functions of dopamine receptors and four signalling pathways (Parkinson's disease, Alzheimer's disease, Huntington's disease and long-term depression) related to both diseases; these warrant further investigation. Our results illustrate the landscape of the novel molecular substructures between DM and BC, which may support a new model for complex disease classification and rational therapies for multiple diseases.
糖尿病(DM)和乳腺癌(BC)可同时出现在相同患者群体中,但其之间的分子关系仍不清楚。在本研究中,我们构建了基因网络并使用模块化分析方法来研究这两种疾病及一种疾病亚型的多维度特征。分别应用文本搜索引擎(安捷伦文献搜索2.71)和MCODE软件来验证潜在子网并划分模块。从《人类孟德尔遗传在线》数据库中鉴定出总共793个与DM相关的基因、386个2型糖尿病(T2DM)基因和873个与BC相关的基因。对于DM和BC,共鉴定出99个重叠基因、9个模块、29个生物学过程和7条通路。同时,对于T2DM和BC,鉴定出56个重叠基因、5个模块、20个生物学过程和12条通路。基于对这两种疾病前10个非重叠模块的基因本体功能富集分析,它们之间有10种生物学功能和5条通路重叠。糖鞘脂和溶酶体通路验证了与DM和BC均相关的细胞死亡分子机制。我们还鉴定出多巴胺受体的新生物学功能以及与这两种疾病均相关的四条信号通路(帕金森病、阿尔茨海默病、亨廷顿病和长时程抑制);这些有待进一步研究。我们的结果阐明了DM和BC之间新型分子亚结构的全貌,这可能为复杂疾病分类和多种疾病的合理治疗提供新模型。