Advances in the pathogenesis and clinical application prospects of tumor biomolecules in keloid

Abstract

Keloid scarring is a kind of pathological healing manifestation after skin injury and possesses various tumor properties, such as the Warburg effect, epithelial–mesenchymal transition (EMT), expression imbalances of apoptosis-related genes and the presence of stem cells. Abnormal expression of tumor signatures is critical to the initiation and operation of these effects. Although previous experimental studies have recognized the potential value of a single or several tumor biomolecules in keloids, a comprehensive evaluation system for multiple tumor signatures in keloid scarring is still lacking. This paper aims to summarize tumor biomolecules in keloids from the perspectives of liquid biopsy, genetics, proteomics and epigenetics and to investigate their mechanisms of action and feasibility from bench to bedside. Liquid biopsy is suitable for the early screening of people with keloids due to its noninvasive and accurate performance. Epigenetic biomarkers do not require changes in the gene sequence and their reversibility and tissue specificity make them ideal therapeutic targets. Nonetheless, given the ethnic specificity and genetic predisposition of keloids, more large-sample multicenter studies are indispensable for determining the prevalence of these signatures and for establishing diagnostic criteria and therapeutic efficacy estimations based on these molecules.

The Role of Intercellular Interactions in the Formation of Keloid Scars

“…There is also an increase in the number of antigen-presenting cells -Langerhans cells (LCs), epidermal inflammatory dendritic cells (IDEC) and macrophages. Mast cell degranulation is observed, as in the studies of other authors [3,14]. The regenerative process in the skin after damage is accompanied by its alteration and remodeling, the number of CD68 and CD163 cells increases and then decreases, which is caused by chronic inflammation.…”

“…The biopsy samples of keloid scars in 43 patients of the same age group after cosmetic surgeries (29) and burns (14) were studied. The skin of 3 patients after surgical operations not associated with skin lesions in the same age group was used as a control.…”

CD74+fibroblasts proliferate upon mechanical stretching to promote angiogenesis in keloid

“…To further dissect the heterogeneity of the fibroblast population, all fibroblasts (a total of 72,767 cells) were re-clustered to obtain 11 fibroblast subtypes with different marker genes (Figures 2A-2B). Since keloid fibroblasts were previously divided into four categories with distinct functions (18)(19)(20)(21)(22)(23), we examined the relationship between our fibroblast subtypes and the prior classification. Subtypes 0, 1, 2, and 3 in our study were positive for POSTN expression, a marker of the previously defined mesenchymal fibroblasts (Supplementary figure 1A).…”

The deubiquitinating enzyme USP37 promotes keloid fibroblasts proliferation and collagen production by regulating the c‐Myc expression

“…Keloid is a group of pathological fibroproliferative skin disorders with unremitting extracellular matrix (ECM) accumulation, remodelling, and stiffness. 1 , 2 Although the pathogenesis of keloid is complex, strong genetic predisposition, growth factors' profile alteration, collagen turnover, and higher stretching tension contribute to keloid formation and development. 3 , 4 , 5 Surgery, steroid, and radiation treatment are recommended in clinics, while the high recurrence and accompanying psychological distress still pose a challenge for affected patients.…”

“…Keloid is a group of pathological fibroproliferative skin disorders with unremitting extracellular matrix (ECM) accumulation, remodelling, and stiffness 1,2 . Although the pathogenesis of keloid is complex, strong genetic predisposition, growth factors' profile alteration, collagen turnover, and higher stretching tension contribute to keloid formation and development 3‐5 .…”