High expression of SERPINE1 and CTSL in keratinocytes in pressure injury caused by ischemia-reperfusion injury.

Introduction: Pressure Injury (PI) is a complex disease process which is influenced by multiple factors, among which ischemia-reperfusion (I/R) injury is closely related to the progression of PI. But its biomarkers are still unclearly. Understanding its physiological mechanisms and related molecular biomarkers is a key to developing effective prevention and therapeutic strategies.

Methods: This study through obtained the candidate genes of the differentially expressed genes (DEGs) from the PI rat model by transcriptome sequencing, PI single-cell sequencing database, and genes related to I/R injury from GeneCards database to analyze and screen prognostic related target genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genomes (KEGG) pathway analysis were performed using clusterProfiler package, and a protein-protein interaction (PPI) network was constructed to identify hub genes. The genes related to I/R injury were identified and analyzed using three machine learning algorithms. Then, the hub genes were evaluated using nomogram and receiver operating characteristic (ROC) curves, and validated using immunohistochemistry in the PI rat model.

Results: There were finally 7 candidate genes obtained from the intersection of the three datasets. GO and KEGG pathway analysis revealed that the DEGs were enriched in complement and coagulation cascades, and the keratinocyte differentiation is a significant factor. Then, two hub genes Serine protease inhibitor clade E member 1 (SERPINE1) and Cathepsin L (CTSL) were identified through three machine learning algorithms. The two hub genes were indicated had a high prognosis value by nomogram and ROC curves. SERPINE1 and CTSL both play crucial roles in vasculogenesis, coagulation and degradation of the extracellular matrix, which is essential for wound healing. The results of immunohistochemistry demonstrated that SERPINE1 and CTSL are significantly upregulated in skin tissue from PI caused by I/R injury, and their mRNA expression levels significantly correlate with PI outcomes.

Conclusion: According to our research we referred that the SERPINE1 and CTSL might be the potential biomarkers of PI.