Identification of signature genes of Dilated cardiomyopathy Using Integrated bioinformatics analysis

Dilated cardiomyopathy (DCM) is characterized by left ventricular or biventricular enlargement with systolic dysfunction. To date, the underlying molecular mechanisms of dilated cardiomyopathy pathogenesis have not been fully elucidated, although some insights have been presented. In this study, we combined public database resources and a doxorubicin-induced DCM mouse model to explore the significant genes of DCM in full depth. We first retrieved six DCM-related microarray datasets from the GEO database using several keywords. Then we used the "LIMMA" (linear model for microarray data) R package to filter each microarray for differentially expressed genes (DEGs). Robust rank aggregation (RRA), an extremely robust rank aggregation method based on sequential statistics, was then used to integrate the results of the six microarray datasets to filter out the reliable differential genes. To further improve the reliability of our results, we established a doxorubicin-induced DCM model in C57BL/6N mice, using the "DESeq2" software package to identify DEGs in the sequencing data. We cross-validated the results of RRA analysis with those of animal experiments by taking intersections and identified three key differential genes (including Bex1, RGCC and VSIG4) associated with DCM as well as many important biological processes (extracellular matrix organization, extracellular structural organization, sulphur compound binding, and extracellular matrix structural components) and a signalling pathway (HIF-1 signalling pathway). Six male C57BL/6N mice were randomly divided into two groups, three in the control group and three in the DCM group. Doxorubicin was injected intraperitoneally to establish the model of dilated cardiomyopathy and controls were given equal amounts of saline. After determining the success of the model, heart tissues were collected and sequenced on MGISEQ-T7 to obtain 150bp paired-end reads.