Bulk RNA sequencing identifies biomarkers for mitochondrial and programmed cell death in keloids

The treatment of keloids (KD) remains challenging. This study focuses on the interplay between mitochondrial dynamics with programmed cell death (PCD) mechanisms in KD.

Bulk RNA sequencing was performed to identify differentially expressed genes (DEGs) and to investigate the most relevant module genes between KD and control samples. Candidate genes were derived from DEGs, weighted gene co-expression network analysis module genes, PCD-related genes, and mitochondria-related genes. Screening employed two complementary machine learning-based approaches to pinpoint KD biomarkers, followed by comprehensive characterization of their biological functions, network properties, and drug interaction potential. Finally, the differentially infiltrated immune cells in the KD group were analyzed.

In this preliminary exploratory study based on 24 samples (12 KD vs. 12 controls) without independent external validation, three biomarkers were identified. All biomarkers were involved in oxidative phosphorylation and ribosome function. Subsequently, 4 miRNAs and 10 transcription factors (TFs) were predicted; 6 TFs were predicted by PRDX4, and 58 miRNAs and 10 TFs were predicted by PDK2. In addition, there were six different immune cells in the KD and control groups, such as central memory CD8⁺ T cells. Finally, bisphenol A demonstrated strong binding affinity for the biomarkers in molecular docking. However, due to its well-documented multisystem toxicity, it has no direct clinical therapeutic value. Therefore, bisphenol A should be considered solely as a structural probe for mechanistic studies rather than a therapeutic candidate.

This study identified UQCRC1, PRDX4, and PDK2 as candidate biomarkers for keloids (KD), providing theoretical support for elucidating the regulatory mechanisms of mitochondria and programmed cell death in keloids. All conclusions were based solely on bioinformatic analyses without in vitro or in vivo experimental validation, thus the findings remain hypothetical and require rigorous confirmation in future studies.