Bioinformatics analysis reveals the changes of peroxisome proliferator-activated receptor (PPAR) pathway in the development of Marjolin ulcers

Abstract

Objective: This study aimed to explore the molecular mechanisms underlying MU development. Methods: Six MU and matched para-cancerous scar tissues were collected and subjected to transcriptome sequencing. Differentially expressed genes (DEGs) were screened, followed by function enrichment analysis. Gene set enrichment analysis (GSEA) was performed to investigate changes in pathways. Expression patterns of hub genes were confirmed by quantitative RT–PCR. Results: A total of 1109 DEGs were identified between MU and para-cancerous scar tissues, including 471 upregulated and 638 downregulated genes. These DEGs mainly participated in extracellular matrix organization-related pathway, cytokine−cytokine receptor interaction, cytokine activity, and IL-17 signalling pathway. GSEA revealed 48 significantly altered pathways. Four common pathways were identified in different enrichment analyses, including PPAR signalling pathway. Among the genes in the PPAR pathway, 18 DEGs were found. Upstream transcription factors RXRG and PPARG were downregulated, while downstream target genes FABP6, OLR1, and MMP1 were upregulated, and FABP3, LPL, and ADIPOQ were downregulated. These results were confirmed by quantitative RT–PCR. Conclusions: PPARγ-mediated PPAR signalling pathway is important during the development of MU. This study promotes future research on the molecular mechanisms of MU and provides novel insights for the prevention and treatment of this disease. Highlights: A total of 1109 DEGs were identified in MU tissue. These DEGs were mainly involved in extracellular matrix organization and inflammation-associated pathways. Various enrichment analyses identified four common pathways, including the PPAR signalling pathway.

Keywords

• marjolin ulcer
• scar squamous cell carcinomas
• ppar signalling pathway