Convergence and divergence of genetic and modular networks between diabetes and breast cancer.
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.
Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China.
Xiaoxu
X
Zhang
Yingying
Y
Zhang
Yanan
Y
Yu
Jun
J
Liu
Ye
Y
Yuan
Yijun
Y
Zhao
Haixia
H
Li
Jie
J
Wang
Zhong
Z
Wang
D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D015897:Comorbidity; D019295:Computational Biology / Q000379:methods*; D030541:Databases, Genetic; D003920:Diabetes Mellitus / Q000453:epidemiology / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D006801:Humans; D008957:Models, Genetic; D015398:Signal Transduction / Q000235:genetics*; D059467:Transcriptome / Q000235:genetics
breast cancer; diabetes; gene interaction network; modularized analysis; type 2 diabetes