Integrated Analysis of Ulcerative Colitis Revealed an Association between PHLPP2 and Immune Infiltration

Abstract

Ulcerative colitis (UC) is a progressive intestine inflammatory disease that is prone to recur. Herein, we utilize microarray technology and bioinformatics to reveal the underlying pathogenesis of UC and provide novel markers. Colonic biopsies were taken from eight UC patients and eight healthy controls. Three differentially expressed miRNAs (DEMIs) and 264 differentially expressed genes (DEGs) were screened using mRNA and miRNA microarray. Most DEGs were significantly associated with immune response and were markedly enriched in the IL-17 signaling pathway. Among the target genes of DEMIs, PHLPP2 overlapped with DEGs and the downregulation of PHLPP2 group was mainly involved in the epithelial–mesenchymal transition. PHLPP2 was downregulated in UC patients, which was validated in 5 GEO datasets and qRT-PCR. The ROC curve demonstrated that PHLPP2 has a perfect ability to distinguish UC patients from healthy controls. Moreover, PHLPP2 was low expression in patients with active UC. CIBERSORT algorithm indicated that the abundance of gamma delta T cells ( $P=0.04$ ), M0 macrophages ( $P=0.01$ ), and activated mast cells ( $P<0.01$ ) was significantly greater than that of the control group. The Spearman correlation analysis showed that PHLPP2 was positively correlated with the proportion of activated NK cells ( $\text{rho}=0.62$ , $P=0.013$ ) and Tregs ( $\text{rho}=0.55$ , $P=0.03$ ), but negatively correlated with those of activated mast cells ( $\text{rho}=-0.8$ , $P<0.01$ ) and macrophages ( $\text{rho}=-0.73$ , $P<0.01$ ). These results indicate that PHLPP2 is associated with immune cells in the pathogenesis of UC, as well as provide new prospects and future directions of investigation.