Identification and validation of mitotic catastrophe-associated biomarkers for keloid.

PURPOSE: Exploring the role of mitotic catastrophe-related genes (MCRGs) in the development of keloid, a benign skin disorder.

METHODS

Differentially expressed genes (DEGs) between keloid and normal tissues were identified. Candidate genes at the intersection of DEGs and MCRGs were selected. Protein-protein interaction network, machine learning, and expression analyses allowed the identification of keloid-associated biomarkers. Nomogram construction, Gene Set Enrichment Analysis (GSEA), and immune cell infiltration, molecular regulatory network, drug prediction, and molecular docking analyses were conducted. Biomarker expression in clinical samples was then experimentally validated.

PRINCIPAL

RESULTS

Protein phosphatase 1 catalytic subunit alpha (PPP1CA) and nuclear distribution C (NUDC) were determined to be the biomarkers, and the nomogram demonstrated their effective predictive potential for keloid. A higher expression of PPP1CA and NUDC was associated with the GSEA gene sets NEUTROPHIL_DEGRANULATION/WP_TRANSLATION_FACTORS and GLUCONEOGENESIS/GLUCOSE_METABOLIC_PROCESS, respectively. Analysis of immune cell infiltration into keloid tissue revealed high correlation between the abundance of specific T-cell populations and the biomarkers. The microRNAs hsa-miR-31315b/hsa-miR-6856-5p and hsa-miR-4743-3p/hsa-miR-8089 were found to be associated with PPP1CA and NUDC, respectively. Furthermore, six transcription factors, including specificity protein 1 and erythroblast transformation specific like-1, were identified to regulate the two biomarkers. PPP1CA exhibited favorable binding affinity toward cantharidin, and NUDC exhibited favorable binding affinity toward latamoxef. These findings were preliminarily validated via in vitro expression analysis.

MAJOR

CONCLUSION

The two MCRGs PPP1CA and NUDC were identified as promising biomarkers with potential roles in keloid pathogenesis and as therapeutic targets.