Gene Network Analysis of Cardiac Allograft Vasculopathy in Heart Transplantation through Messanger RNA Expression Profile

Purpose The aim of this preliminary study was to perform exploration, integration and analysis of large-scale, genome-wide data with transcriptome platform to evaluate, without a selection bias, the expression profile of mRNA on FFPE-EMBs of heart transplanted patients affected by CAV. Methods Our cohort of study was composed by 11 adult HTx patients. We selected FFPE-EMB from heart transplanted patients characterized by the presence of CAV (n=7), and control group (n=4) with absence of rejection and CAV, with age/sex match and same time interval from HTx. We performed a pangenomic expression microarray profiling (Clariom S assay) without a bias of transcript selection. Bioinformatic mRNA expression analysis on distinct FFPE-EMBs samples was performed using enrichment analysis software: EnrichR, an online software application including gene-set libraries to rank enriched terms; and GSEA (gene set enrichment analysis) a priori-free bioinformatic analytical tool for interpreting gene expression data. Results Through EnrichR and GSEA analysis we recognized specific patterns of expression of mRNA. Within the CAV group, in GSEA analysis, 700 gene sets were highlighted. 118 gene sets were significantly enriched at FDR Conclusion These preliminary data from categories emerged through enrichment analysis, suggested the presence of one prevalent mechanism correlated to CAV and related to enrichment in pathways connected to cell cycle dysregulation and DNA/chromatin metabolism. While these categories seemed to be silent in control group without CAV, a downregulation of pathways’ genes related more to neuronal tropism and cardiac contraction was observed. All these aspects may help us in highlighting novel and not-yet investigated molecular pathways involved in CAV development.