Prediction of co-expression genes and integrative analysis of gene microarray and proteomics profile of Keshan disease

Abstract

Keshan disease (KD) is a kind of endemic cardiomyopathy which has a high mortality. However, molecular mechanism in the pathogenesis of KD remains poorly understood. Serum samples were collected from 112 KD patients and 112 normal controls. Gene microarray was used to screen differently expressed genes. Genevestigator was applied to forecast co-expression genes of significant gene. iTRAQ proteomics analysis was used to verify significant genes and their co-expression genes. GO, COG, IPA and STRING were applied to undertake function categorization, pathway and network analysis separately. We identified 32 differentially expressed genes; IDH2, FEM1A, SSPB1 and their respective 30 co-expression genes; 68 differential proteins in KD. Significant proteins were categorized into 23 biological processes, 16 molecular functions, 16 cellular components, 15 function classes, 13 KD pathways and 1 network. IDH2, FEM1A, SSBP1, CALR, NDUFS2, IDH3A, GAPDH, TCA Cycle II (Eukaryotic) pathway and NADP repair pathway may play important roles in the pathogenesis of KD.

The Role of Cullin-RING Ligases in Striated Muscle Development, Function, and Disease

“…Biochemical and microscopy analyses in muscle cells showed that Fem1a localizes within the mitochondria and is up-regulated in the heart upon ischemia-reperfusion injury [ 197 ]. Fem1 proteins are also increased in patients with Keshan disease, a subtype of cardiomyopathy [ 198 ]. The association of Fem1 proteins with this disease indicates that these cullin-2 adapter proteins play important roles for cardiac homeostasis.…”

Selenium-Related Transcriptional Regulation of Gene Expression

“…Pathway analysis revealed 52 pathways, of which hypoxia-inducible factor-1α and apoptosis pathways were likely to play a role in the selenium-associated functions [ 115 ]. A study combining a custom-made microarray, containing 78 probes previously differentially expressed genes in Keshan disease, analyses of peripheral blood mononuclear cell RNA samples obtained from 100 Keshan disease patients and 100 normal controls, and mass spectrometric proteomic analyses of peripheral blood sera of Keshan patients and controls indicated that there are numerous functional pathways and cellular systems associated with the differentially expressed genes and proteins [ 116 ]. The limitations of these studies are the fact that the selenium status of the individuals was not known.…”

Selenium-Related Transcriptional Regulation of Gene Expression

“…Pathway analysis revealed 52 pathways, of which hypoxia-inducible factor-1 and apoptosis pathways are likely to play a role in selenium-associated functions [92]. A study combining custom-made microarray (containing 78 probes previously differentially expressed genes in Keshan disease) analyses performed for peripheral blood mononuclear cell RNA samples obtained from 100 Keshan disease patients and 100 normal controls, and mass spectrometric proteomic analyses of peripheral blood sera indicated that there are numerous functional categories associated with differentially expressed genes and proteins [93]. The limitations of these studies are the fact that the selenium status of the individuals was not known.…”