Dataset Information

Spatio-temporal analysis of type 2 diabetes mellitus based on differential expression networks.

ABSTRACT: T2DM is complex in its dynamical dependence on multiple tissues, disease states, and factors' interactions. However, most existing work devoted to characterizing its pathophysiology from one static tissue, individual factors, or single state. Here we perform a spatio-temporal analysis on T2DM by developing a new form of molecular network, i.e. 'differential expression network' (DEN), which can reflect phenotype differences at network level. Static DENs show that three tissues (white adipose, skeletal muscle, and liver) all suffer from severe inflammation and perturbed metabolism, among which metabolic functions are seriously affected in liver. Dynamical analysis on DENs reveals metabolic function changes in adipose and liver are consistent with insulin resistance (IR) deterioration. Close investigation on IR pathway identifies 'disease interactions', revealing that IR deterioration is earlier than that on SlC2A4 in adipose and muscle. Our analysis also provides evidence that rising of insulin secretion is the root cause of IR in diabetes.

SUBMITTER: Sun SY

PROVIDER: S-EPMC3721080 | biostudies-other | 2013

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Spatio-temporal analysis of type 2 diabetes mellitus based on differential expression networks.

Sun Shao-Yan SY Liu Zhi-Ping ZP Zeng Tao T Wang Yong Y Chen Luonan L

Scientific reports 20130101

T2DM is complex in its dynamical dependence on multiple tissues, disease states, and factors' interactions. However, most existing work devoted to characterizing its pathophysiology from one static tissue, individual factors, or single state. Here we perform a spatio-temporal analysis on T2DM by developing a new form of molecular network, i.e. 'differential expression network' (DEN), which can reflect phenotype differences at network level. Static DENs show that three tissues (white adipose, ske ...[more]

PMID: 23881262

Similar Datasets

Project description:BackgroundType 2 Diabetes Mellitus (T2DM) is an independent risk factor of hepatocellular carcinoma (HCC). However, the related genes and modules to hepatocarcinogenesis and progression in T2DM remain unclear.MethodsThe microarray data from Gene Expression Omnibus (GEO) were analyzed to screen differentially expressed genes (DEGs) of T2DM and HCC dataset. Then, weighted gene co-expression network analysis (WGCNA) was performed on these DEGs to detect the modules and genes, respectively. Common genes in modules with clinical interests of T2DM and HCC were obtained and annotated via GOSemSim package and Metascape. Genes related to late-stage HCC and high glycated haemoglobin (HbA1c) were also identified. These genes were validated by UALCAN analysis and univariate cox regression based on The Cancer Genome Atlas (TCGA). Finally, another two independent datasets were applied to confirm the results of our study.ResultsA total of 1288 and 1559 DEGs of T2DM and HCC were screened, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment revealed several shared pathways in two diseases, such as pathways in cancer and metabolism. A total of 37 common genes correlated with T2DM and HCC were then identified with WGCNA. Furthermore, 12 genes from modules associated with late-stage HCC and high HbA1c were regarded as hub genes. Among these genes, 8 genes associated with tumor invasion and metastasis were validated by UALCAN analysis. Moreover, downregulations of ACAT1, SLC2A2, PCK1 and ABAT were significantly associated with poorer prognosis in HCC patients with elevated HbA1c. Additionally, the expressions of PCK1 and ABAT were raised in HepG2 cells pre-treated with metformin and phenformin.ConclusionsThe present study confirmed several metabolic genes related to hyperglycemia and malignant tumor, which may provide not only new insights into the pathogenesis of hepatocarcinogenesis and progression in T2DM, but also novel therapeutic targets for T2DM patients with HCC in the future.

Dataset Information

Spatio-temporal analysis of type 2 diabetes mellitus based on differential expression networks.

Publications

Spatio-temporal analysis of type 2 diabetes mellitus based on differential expression networks.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets