Identification of Hub Genes Associated with Abnormal Endothelial Function in Early Coronary Atherosclerosis.

Abnormal coronary endothelial function is an important step in the development of atherosclerosis. Coronary atherosclerosis is one of the main causes of death worldwide. We constructed a co-expression network to identify hub genes associated with abnormal coronary endothelial function in early coronary atherosclerosis. In brief, we used the GSE132651 dataset from the gene expression omnibus database. The top 5000 genes with greatest variances were used for weighted gene co-expression network analysis, and the module most strongly correlated with abnormal coronary endothelial function was chosen as key module. Functional enrichment analysis was performed for genes in the key module, a protein-protein interaction network was constructed to find hub genes, and gene set enrichment analysis (GSEA) was also performed. Genes were classified into 7 modules, with the midnightblue module being the one that was most related to abnormal coronary endothelial function and containing genes enriched in DNA replication, cell cycle, nucleotide excision repair, and Human T-cell leukemia virus 1 infection. We identified nine hub genes (HOXC5, PRND, PADI3, RC3H1, DAPP1, SIT1, DRICH1, GPRIN2, and RHO), which differently expressed in abnormal and normal coronary endothelial function samples. GSEA suggested that samples associated with abnormal coronary endothelial function and highly expressed hub genes were linked with immune, coagulation, hypoxia, and angiogenesis processes. These hub genes, their expression pattern, and pathways may be involved in the development of abnormal coronary endothelial function and promotion of early coronary atherosclerosis.

Identification of Hub Genes and MicroRNAs Associated With Idiopathic Pulmonary Arterial Hypertension by Integrated Bioinformatics Analyses.

OBJECTIVE: The aim of this study is the identification of hub genes associated with idiopathic pulmonary arterial hypertension (IPAH). MATERIALS AND METHODS: GSE15197 gene expression data was downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified by screening IPAH patients and controls. The 5,000 genes with the greatest variances were analyzed using a weighted gene co-expression network analysis (WGCNA). Modules with the strongest correlation with IPAH were chosen, followed by a functional enrichment analysis. Protein-protein interaction (PPI) networks were constructed to identify hub gene candidates using calculated degrees. Real hub genes were found from the overlap of DEGs and candidate hub genes. microRNAs (miRNAs) targeting real hub genes were found by screening miRNet 2.0. The most important IPAH miRNAs were identified. RESULTS: There were 4,395 DEGs identified. WGCNA indicated that green and brown modules associated most strongly with IPAH. Functional enrichment analysis showed that green and brown module genes were mainly involved in protein digestion and absorption and proteoglycans in cancer, respectively. The top ten candidate hub genes in green and brown modules were identified, respectively. After overlapping with DEGs, 11 real hub genes were identified: EP300, MMP2, CDH2, CDK2, GNG10, ALB, SMC2, DHX15, CUL3, BTBD1, and LTN1. These genes were expressed with significant differences in IPAH versus controls, indicating a high diagnostic ability. The miRNA-gene network showed that hsa-mir-1-3p could associate with IPAH. CONCLUSION: EP300, MMP2, CDH2, CDK2, GNG10, ALB, SMC2, DHX15, CUL3, BTBD1, and LTN1 may play essential roles in IPAH. Predicted miRNA hsa-mir-1-3p could regulate gene expression in IPAH. Such hub genes may contribute to the pathology and progression in IPAH, providing potential diagnostic and therapeutic opportunities for IPAH patients.