Metabolism‐related biomarkers, molecular classification, and immune infiltration in diabetic ulcers with validation

Abstract

Diabetes mellitus (DM) can lead to diabetic ulcers (DUs), which are the most severe complications. Due to the need for more accurate patient classifications and diagnostic models, treatment and management strategies for DU patients still need improvement. The difficulty of diabetic wound healing is caused closely related to biological metabolism and immune chemotaxis reaction dysfunction. Therefore, the purpose of our study is to identify metabolic biomarkers in patients with DU and construct a molecular subtype‐specific prognostic model that is highly accurate and robust. RNA‐sequencing data for DU samples were obtained from the Gene Expression Omnibus (GEO) database. DU patients and normal individuals were compared regarding the expression of metabolism‐related genes (MRGs). Then, a novel diagnostic model based on MRGs was constructed with the random forest algorithm, and classification performance was evaluated utilizing receiver operating characteristic (ROC) analysis. The biological functions of MRGs‐based subtypes were investigated using consensus clustering analysis. A principal component analysis (PCA) was conducted to determine whether MRGs could distinguish between subtypes. We also examined the correlation between MRGs and immune infiltration. Lastly, qRT‐PCR was utilized to validate the expression of the hub MRGs with clinical validations and animal experimentations. Firstly, 8 metabolism‐related hub genes were obtained by random forest algorithm, which could distinguish the DUs from normal samples validated by the ROC curves. Secondly, DU samples could be consensus clustered into three molecular classifications by MRGs, verified by PCA analysis. Thirdly, associations between MRGs and immune infiltration were confirmed, with LYN and Type 1 helper cell significantly positively correlated; RHOH and TGF‐β family remarkably negatively correlated. Finally, clinical validations and animal experiments of DU skin tissue samples showed that the expressions of metabolic hub genes in the DU groups were considerably upregulated, including GLDC, GALNT6, RHOH, XDH, MMP12, KLK6, LYN, and CFB. The current study proposed an auxiliary MRGs‐based DUs model while proposing MRGs‐based molecular clustering and confirmed the association with immune infiltration, facilitating the diagnosis and management of DU patients and designing individualized treatment plans.

Enhancing wound healing and overcoming cisplatin resistance in ovarian cancer

“…On fibroblast cultures, wound repair assay was conducted subsequent to transfection. To determine the rate of wound closure, a cut was made in the cell monolayer and the migration of fibroblasts into the wound area will be quantified and monitored 24–26 …”

“…To determine the rate of wound closure, a cut was made in the cell monolayer and the migration of fibroblasts into the wound area will be quantified and monitored. 24 , 25 , 26 …”

“…Involving tissue repair and regeneration, wound healing is an intricate biological process that necessitates a delicate equilibrium of cellular activities, such as proliferation, differentiation and the elimination of damaged cells 23,24 . By modulating the turnover of cellular components, autophagy affects these processes and, consequently, the quality and efficiency of wound repair 25 . Important cellular processes, including fibroblast activation, pain regulation and collagen deposition, can be disrupted by dysregulated autophagy, resulting in compromised wound healing.…”

“… 23 , 24 By modulating the turnover of cellular components, autophagy affects these processes and, consequently, the quality and efficiency of wound repair. 25 Important cellular processes, including fibroblast activation, pain regulation and collagen deposition, can be disrupted by dysregulated autophagy, resulting in compromised wound healing. Gaining a comprehensive understanding of the complex interplay between autophagy and wound healing yields significant knowledge for the development of therapeutic approaches that promote improved tissue regeneration and repair, particularly in pathological states characterized by autophagy disruption.…”