A Nomogram with the Keloid Activity Assessment Scale for Predicting the Recurrence of Chest Keloid after Surgery and Radiotherapy.

BACKGROUND: Patients with chest keloids undergoing surgery and adjuvant radiotherapy still have a high recurrence rate, which is a critical problem. The level of keloid activity has not been studied, and a nomogram model for predicting keloid recurrence has not been established in previous studies. METHODS: A total of 145 patients with chest keloids who underwent surgery and radiotherapy between January 2015 and January 2019 at Peking Union Medical College Hospital were included in our study. Demographic and clinical features and the score of KAAS were analyzed. We compared the area under the curve (AUC) and decision curve analysis (DCA) between KAAS and the Vancouver scar scale (VSS) and established a nomogram model for predicting the risk of recurrence. We used bootstrap and calibration plots to evaluate the performance of the nomogram. RESULTS: The KAAS can predict recurrence in patients with chest keloids after surgery and radiotherapy. Areas under the curve (AUCs) of KAAS and VSS were 0.858 and 0.711, respectively (p < 0.001). Decision curve analysis (DCA) demonstrated that the KAAS was better than the VSS. Complications after treatment may be risk factors for keloid recurrence. We created a nomogram by using complications and KAAS. The AUC was 0.871 (95% CI 0.812-0.930). The ROC of the model's bootstrap was 0.865 and was well calibrated. CONCLUSIONS: The KAAS can be used to predict the recurrence and we developed a nomogram for predicting the recurrence of chest keloids after surgery and adjuvant radiotherapy. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Labiaplasty in Adolescents: Indications and Treatment Protocol.

BACKGROUND: Adolescents constitute a unique group of labia minora hypertrophy patients, but the necessity and benefits of labiaplasty for adolescents remain controversial. OBJECTIVES: The purpose of this study was to summarize the surgical indications, the details of the treatment procedure, postoperative complications, and therapeutic outcomes of labiaplasty in the adolescent population. METHODS: A retrospective chart review was performed of adolescent patients aged <18 years old who underwent labiaplasty between January 2016 and May 2022. Patient characteristics, surgical method, concomitant procedures, procedure side, operative time, complications, and follow-up data were recorded. RESULTS: A total of 12 patients aged <18 years were included in this study. All procedures were performed for functional reasons. The mean [standard deviation] operative time was 61.75 [20.77] minutes (range, 38-114 minutes). Unilateral labia minora hematoma within 24 hours occurred in 2 of the 12 patients (16.7%) and surgical evacuations were performed immediately. All patients were followed up electronically at 42.33 [16.88] months (range, 14-67 months). Notably, 83.33% (10/12) of patients reported being very satisfied, and 16.67% (2/12) of patients were satisfied. There was no patient dissatisfaction. Preoperative discomfort was completely resolved in 9 patients (75.00%) and significantly improved in 3 patients (25.00%). Furthermore, no patients indicated that symptoms were not improved or made worse. CONCLUSIONS: In the adolescent population, severe hypertrophy of the labia minora and the clitoral hood will cause discomfort, affecting the quality of life and mental health. Therefore, labiaplasty is a safe and effective procedure in adolescents to improve genital appearance and quality of life.

Risk factors associated with keloid infections: A five-year retrospective study.

Keloid infections reduce patient-reported quality of life greatly. Characteristics and risk factors of keloid infections have not been thoroughly studied. So, a retrospective cohort study was conducted focusing on the potential risk factors, microbiologic cultures and histological findings. Keloid patients consulting for surgical interventions were included in this study. Data were collected from their electronic medical records. 564 patients were recruited with the keloid infection rate being 22.4%. For adult patients, age above 40 years (OR, 2.84; P = .000), disease duration of 12 years or more (OR, 3.03; P = .000), the number of keloids over 3 (OR, 1.59; P = .050) and the presence of family history (OR, 1.91; P = .027) were significantly associated with keloid infections. Suppurative keloids were located mostly in thorax (61.79%). For the under-age subgroup(n = 25), family history was frequently seen in patients with infections. Microbiologic cultures revealed a mixed spectrum of bacteria including Staphylococcus (25%), Actinomyces (30%) and Prevotella (10%). The rate of epidermoid cysts was 19.7% in histological examination. Age > 40 years, disease duration ≥12 years, the number of keloids >3 and the presence of family history are risk factors for keloid infections.

Histology and Vascular Architecture Study of Keloid Tissue to Outline the Possible Terminology of Keloid Skin Flaps.

BACKGROUND: Using the keloid "epidermis" to cover a wound is widely used during treatment for keloids. Many flap terminologies have been used in literature. However, the definition of the flap is not well established. Here, we refined the definition of the flap and associated terminology and explored the survival mechanism of the 'flap' through histological analysis and blood supply studying. METHODS: Histology and vascular study of keloid was carried out with keloid and its surrounding normal skin tissue which were collected from keloid patients following keloid resection operations. The histological structures and thicknesses of epidermal and subepidermal of the keloids were analyzed and measured using hematoxylin & eosin (H&E) staining. Vascular density and blood perfusion in the subepidermal layer of keloids (KDS) were analyzed using CD31 immunohistochemical staining and a laser speckle contrast imaging system (LSCI), respectively. The vascular network in KDS was visualized by CD31 immunofluorescence staining and three-dimensional reconstruction. RESULTS: 29 pieces of keloid and its surrounding normal skin tissue sample from ten patients were collected. Keloid samples were about 2 cm wide and 5 cm long. The normal skin samples were about 2 to 3 mm in width. The thickness of epidermal layer of keloids was (136.4 ± 35.3) µm, and the thickness of epidermal layer of surrounding normal skin was (78.8 ± 13.9) µm. There was statistical thickness difference between the two layers, t(20) = 7.469, P < 0.001. The total thickness of keloid epidermal and subepidermal layers was 391.4 ± 2.3 µm. The vascular density (13.9 ± 3.4/field) and blood flow perfusion (132.7 ± 31.3) PU in KDS were greater than that of surrounding normal skin (7.8 ± 2.3/field, 73.9 ± 17.9 PU), P < 0.001. Horizontally distributed vessels with several vertical branches were observed in 3D vascular network reconstruction. CONCLUSION: The epidermal layer of keloid is thicker than that of surrounding normal skin. There is a vascular network structure under it. The vessels mainly locate at a depth of about 150 to 400 µm from the surface of keloid epidermis, randomly distribute and run parallel to the epidermis. Based on these characteristics which may ensure an adequate blood supply, we propose the concept of a "keloid subepidermal vascular network flap." LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Clinical Observation of Subepidermal Vascular Network Flaps in Keloid Patients.

BACKGROUND: There are many different keloid treatment modalities. One surgical technique is to keep the "shell" of the keloid to cover the defect. We named this "shell" keloid subepidermal vascular network flap (KSVNF), and we outlined the characteristics of this flap by observing 35 flaps in keloid patients. METHODS: A total of 35 KSVNFs were designed in 15 patients during 2020-2021. All patients underwent the operation and adjuvant radiotherapy as well as hyperbaric oxygen therapy. All flap lengths and widths were recorded, and the blood perfusion of the flaps was measured on the first day postoperation and the day of stitch removal. Flap survival and the quality of flaps were evaluated on the day of stitch removal. All harvested data were analyzed using the R (version 4.0.1) package. RESULTS: The mean blood perfusion on the first day postoperation (pod1) and the day of stitch removal was 120.4013 and 168.6900, respectively (p = 0.02249); 2 flaps had partial necrosis (5.714%). Receiver operating characteristic (ROC) curve analysis showed that when the length/width ratio was less than 1.05, the quality of the flap was good (AUC = 0.724), which suggests that the effective safe length/width ratio was 1.05. CONCLUSION: KSVNF is an applicable method for covering the remaining wound after keloid mass removal with sufficient blood perfusion and adequate skin quality. We recommend that the length/width ratio of the flap design not exceed 1. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The Role of CD28 and CD8+ T Cells in Keloid Development.

Background: A keloid is a benign skin tumor that extends beyond the initial injury area, and its pathologic mechanism remains unclear. Method: High-throughput sequencing data were obtained from normal skin tissue of patients with keloids (Group N) and healthy controls (Group C). Important genes were mined by bioinformatics analysis and identified by RT−qPCR, Western blotting, immunohistochemistry and immunofluorescence assays. The CIBERSORT algorithm was used to convert gene expression information into immune cell information. Flow cytometry was used to verify the key immune cells. Fluorescence-activated cell sorting coculture and CCK8 experiments were used to explore the effect of CD8+ T cells on keloid-associated fibroblasts. Neural network models were used to construct associations among CD28, CD8+ T cells and the severity of keloids and to identify high-risk values. Result: The expression levels of costimulatory molecules (CD28, CD80, CD86 and CD40L) in the skin tissue of patients with keloids were higher than the levels in healthy people (p < 0.05). The number of CD8+ T cells was significantly higher in Group N than in Group C (p < 0.05). The fluorescence intensities of CD28 and CD8+ T cells in Group N were significantly higher than those in Group C (p = 0.0051). The number and viability of fibroblasts cocultured with CD8+ T cells were significantly reduced compared with those of the control (p < 0.05). The expression of CD28 and CD8+ T cells as the input layer may be predictors of the severity of keloids with mVSS as the output layer. The high-risk early warning indicator for CD28 is 10−34, and the high-risk predictive indicator for CD8+ T cells is 13−28. Conclusions: The abnormal expression of costimulatory molecules may lead to the abnormal activation of CD8+ T cells. CD8+ T cells may drive keloid-associated immunosuppression. The expression of CD28 and CD8+ T cells as an input layer may be a predictor of keloid severity. CD28 and CD8+ T cells play an important role in the development of keloids.

Identification of biomarkers in macrophages of atherosclerosis by microarray analysis.

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) refers to a series of diseases caused by atherosclerosis (AS). It is one of the most important causes of death worldwide. According to the inflammatory response theory, macrophages play a critical role in AS. However, the potential targets associated with macrophages in the development of AS are still obscure. This study aimed to use bioinformatics tools for screening and identifying molecular targets in AS macrophages. METHODS: Two expression profiling datasets (GSE7074 and GSE9874) were obtained from the Gene Expression Omnibus dataset, and differentially expressed genes (DEGs) between non-AS macrophages and AS macrophages were identified. Functional annotation of the DEGs was performed by analyzing the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. STRING and Cytoscape were employed for constructing a protein-protein interaction network and analyzing hub genes. RESULTS: A total of 98 DEGs were distinguished between non-AS macrophages and AS macrophages. The functional variations in DEGs were mainly enriched in response to hypoxia, respiratory gaseous exchange, protein binding, and intracellular, ciliary tip, early endosome membrane, and Lys63-specific deubiquitinase activities. Three genes were identified as hub genes, including KDELR3, CD55, and DYNC2H1. CONCLUSION: Hub genes and DEGs identified by using microarray techniques can be used as diagnostic and therapeutic biomarkers for AS.

Multi-omics analyses reveal bacteria and catalase associated with keloid disease.

BACKGROUND: The pathology of keloid and especially the roles of bacteria on it were not well understood. METHODS: In this study, multi-omics analyses including microbiome, metaproteomics, metabolomic, single-cell transcriptome and cell-derived xenograft (CDX) mice model were used to explore the roles of bacteria on keloid disease. FINDINGS: We found that the types of bacteria are significantly different between keloid and healthy skin. The 16S rRNA sequencing and metaproteomics showed that more catalase (CAT) negative bacteria, Clostridium and Roseburia existed in keloid compared with the adjacent healthy skin. In addition, protein mass spectrometry shows that CAT is one of the differentially expressed proteins (DEPs). Overexpression of CAT inhibited the proliferation, migration and invasion of keloid fibroblasts, and these characteristics were opposite when CAT was knocked down. Furthermore, the CDX model showed that Clostridium butyricum promote the growth of patient's keloid fibroblasts in BALB/c female nude mice, while CAT positive bacteria Bacillus subtilis inhibited it. Single-cell RNA sequencing verified that oxidative stress was up-regulated and CAT was down-regulated in mesenchymal-like fibroblasts of keloid. INTERPRETATION: In conclusion, our findings suggest that bacteria and CAT contribute to keloid disease. FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

Multi-omics integrative analysis reveals the role of tumor necrosis factor superfamily member 4 in keloidal scarring.

OBJECTIVES: To identify aberrantly expressed immune molecules in keloids and to explore their possible biologic significance. METHODS: Immune molecules with abnormal expression were identified based on immune gene sequencing of keloids, microarray datasets and high-throughput sequencing datasets and methylation microarray datasets from the Gene Expression Omnibus (GEO) database, and real-time quantitative PCR analysis. RESULTS: Upregulation of tumor necrosis factor superfamily member 4 (TNFSF4) in keloids was identified. Enrichment analysis found that high TNFSF4 expression was associated with immune processes, such as regulation of neutrophil chemotaxis, dendritic cell chemotaxis, and antigen processing and presentation. Single-cell RNA sequencing (scRNA) results suggested that TNFSF4 was upregulated in mesenchymal fibroblasts, which are the critical cells in skin fibrosis. This high expression of TNFSF4 enhanced cell-to-cell interactions in fibrosis-related pathways, including the fibronectin 1 (FN1) and collagen pathways. Mesenchymal fibroblasts expressing TNFSF4 significantly upregulated gene expression in extracellular matrix organization and wound healing processes. CONCLUSIONS: Our study revealed upregulation of the immune molecule TNFSF4 in keloids at the multi-omics level and its effects on intercellular crosstalk and transcriptional profiles of mesenchymal fibroblasts. Investigation of TNFSF4 as an immune checkpoint molecule may represent a new direction for keloid treatment research.

Decoding the molecular landscape of keloids: new insights from single-cell transcriptomics.

Keloids are a fibrotic disease caused by an excessive accumulation of extracellular matrix in the dermis; they have neoplasia-like properties of aggressive growth and high posttreatment recurrence rates. Therefore, it is imperative to gain additional insight into the pathobiology of keloid formation. Single-cell RNA sequencing (scRNA-seq) technology has brought data-driven innovation to understanding the pathogenesis of keloids by breaking the limitations of traditional sequencing technologies to resolve cell composition and to distinguish functional cell subtypes at an unprecedented resolution. The present review aims to cover the application of scRNA-seq technology in keloids and its exploratory findings, including the depiction of the cellular landscape of keloids, fibroblast heterogeneity, the lineage development of Schwann cells and the mesenchymal-activation phenomenon of endothelial cells. Furthermore, scRNA-seq records the transcriptional profiles of fibroblasts and immune cells in a more refined manner, and this gene expression information provides excellent material for inferring intercellular communication networks and lays an important theoretical foundation for future studies.

Deciphering the single-cell transcriptome network in keloids with intra-lesional injection of triamcinolone acetonide combined with 5-fluorouracil.

Objectives: Keloid is a highly aggressive fibrotic disease resulting from excessive extracellular matrix deposition after dermal injury. Intra-lesional injection of triamcinolone acetonide (TAC) in combination with 5-fluorouracil (5-FU) is a commonly used pharmacological regimen and long-term repeated injections can achieve sustained inhibition of keloid proliferation. However, the molecular mechanisms underlying the inhibitory effect on keloids remain insufficiently investigated. Methods and materials: This study performed single-cell RNA sequencing analysis of keloids treated with TAC+5-FU injections, keloids, and skins to explore patterns of gene expression regulation and cellular reprogramming. Results: The results revealed that TAC+5-FU interrupted the differentiation trajectory of fibroblasts toward pro-fibrotic subtypes and induced keloid atrophy possibly by inhibiting the FGF signaling pathway in intercellular communication. It also stimulated partial fibroblasts to develop the potential for self-replication and multidirectional differentiation, which may be a possible cellular source of keloid recurrence. T cell dynamics demonstrated elevated expression of secretory globulin family members, which may be possible immunotherapeutic targets. Schwann cell populations achieved functional changes by increasing the proportion of apoptotic or senescence-associated cell populations and reducing cell clusters that promote epidermal development and fibroblast proliferation. Conclusions: Our findings elucidated the molecular and cellular reprogramming of keloids by intra-lesional injection of TAC+5-FU, which will provide new insights to understand the mechanism of action and therapeutic targets.

Histopathologic study of keloid vascular structures shows the vascular origin pattern of keloid subepidermal vascular network flaps.

BACKGROUND: Keloid subepidermal vascular network flaps (KSVNFs) have achieved satisfactory results in clinical practice. Through this retrospective study, we further examined keloid vascular structure to better understand vascular origin pattern in KSVNFs. METHODS: Paraffin-embedded keloid tissues were stained for CD31. Distances from keloid subepidermal capillaries to the skin surface were measured. The included angle between the pedicle vessels and skin surface (angle PV), as well as the included angle between the keloid margin and skin surface (angle KM), were also measured. The major and minor axes of the capillary in the central areas of keloid (KDC), adjacent skin (AS) and marginal areas of keloid (KDM) were analyzed, and the major:minor axis ratios (M/m) were calculated. Vessels in KSVNF pedicle sites (KDP) were compared with vessels in adjacent skin as a subgroup analysis. RESULTS: Twenty-nine keloid specimens in total were collected. Based on 1630 measured data points, the capillary distance to the skin surface was 387.2±96.7 µm. The angle PV was 70.1±36.6°, and the angle KM was 67.0±18.1°. The major axis of the KDM capillaries was significantly longer than that of KDC and AS (both P < 0.001). The major and minor axes were longer in KDP than in AS (both P < 0.001). CONCLUSION: Suprakeloidal blood vessels are mainly distributed at a depth of 387.2±96.7 µm from the skin. The subepidermal plexus in KSVNF pedicle sites enters the skin at an acute angle and runs parallel to the keloid margin layer. Vessels in keloid marginal areas had crushed vascular lumen, but vessels in KSVNF pedicles did not.

Joint effect of RRP9 and DDX21 on development of colorectal cancer and keloid.

BACKGROUND: Colorectal cancer (CRC) is a common malignancy in the gastrointestinal tract. Keloid refers to abnormal scar tissue that forms on the skin or mucous membrane. The relationship between RRP9 and DDX21 and the two diseases is unclear. METHODS: Download the colorectal cancer dataset GSE134834, GSE206800, GSE209892 and keloid dataset GSE44270 from the GEO database. Differentially expressed genes (DEGs) were screened and weighted gene co-expression network analysis (WGCNA) was performed. The construction and analysis of protein-protein interaction (PPI) network, functional enrichment analysis, gene set enrichment analysis (GSEA). Gene expression heat map was drawn. The comparative toxicogenomics database (CTD) analysis was performed to find diseases most related to core genes. TargetScan screened miRNAs that regulated central DEGs. We conducted experimental validation using Western blotting and Polymerase Chain Reaction (PCR). RESULTS: In the colorectal cancer dataset and the scar tissue dataset, we identified 1380 DEGs and 1000 DEGs, respectively. The enrichment pattern for scar tissue was similar to that of colorectal cancer. We identified two core genes, RRP9 and DDX21. CTD analysis indicated that RRP9 and DDX21 are associated with proliferation, scar tissue, colorectal tumors, scleroderma, and inflammation. We found that the core genes (RRP9 and DDX21) were highly expressed in colorectal cancer and scar tissue samples, while their expression was lower in normal samples. This was further validated through Western blotting (WB) and Polymerase Chain Reaction (PCR). CONCLUSIONS: The higher the expression of RRP9 and DDX21 in colorectal cancer and keloid, the worse the prognosis.

Viewing keloids within the immune microenvironment.

Keloid is a fibrous hyperplastic disease of the skin characterized by excessive collagen deposition. Keloid patients suffer from severe facial damage and psychological burden, but the underlying pathologic mechanism remains unclear. Keloid fibroblasts are often considered the key cell of keloid formation, but the regulation of the immune microenvironment of keloid fibroblasts is poorly understood. The pathogenic roles of macrophages, Tregs, CD8+ T cells, dendritic cells, and natural killer cells in keloids are reviewed and further directions proposed, which may provide a novel window of opportunity for immunotherapy of keloids. Considering the dearth of studies on the function of immune cells related to keloids, the mechanisms of these immune cells in other diseases are further examined herein to provide a reference for future research on the immune microenvironment of keloids.

Identification of a Diagnostic Signature and Immune Cell Infiltration Characteristics in Keloids.

Background: Keloid disorder is a recurrent fibroproliferative cutaneous tumor. Due to the lack of early identification of keloid patients before the formation of keloids, it is impossible to carry out pre-traumatic intervention and prevention for these patients. This led us to identify and determine signatures with diagnostic significance for keloids. Methods: Public series of matrix files were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were calculated from expression profiling data, and the diagnostic signature was identified by constructing a protein-protein interaction (PPI) network. The diagnostic efficacy of the screened signature was assessed by employing receiver operating characteristic (ROC) curves. Furthermore, we calculated the proportion of different immune cells in the gene expression matrix microenvironment by the "ssGSEA" algorithm, and assessed the difference in immune cell abundance between keloids and control groups and the relationship between the signature and immune cell infiltration. Clinical keloid and normal skin tissues were collected, and the expression of the screened diagnostic signature was validated by RT-qPCR and immunohistochemical assay. Results: By screening the key genes in PPI, TGM2 was recognized and validated as a diagnostic signature and the infiltrating abundance of 10 immune cells was significantly correlated with TGM2 expression. Gene ontology enrichment analysis demonstrated that TGM2 and molecules interacting with it were mainly enriched in processes involving wound healing and collagen fiber organization. TGM2 correlated positively with HIF-1A (R = 0.82, p-value = 1.4e-05), IL6 (R = 0.62, p-value = 0.0053), and FN1 (R = 0.66, p-value = 0.0019). Besides, TGM2 was significantly upregulated in clinical keloid samples compared to normal skin tissues. Conclusion: TGM2 may serve as an auxiliary diagnostic indicator for keloids. However, the role of TGM2 in keloids has not been adequately reported in the current literature, which may provide a new direction for molecular studies of keloids.

IL-4 and CCR7 play an important role in the development of keloids in patients with a family history.

BACKGROUND: The occurrence of keloids tends to show family clusters and more severe symptoms in patients with a family history of the condition, but their pathological mechanisms remain unclear. In this study, we aimed to investigate the differences in genetic susceptibility between keloid patients with a family history of keloids and sporadic patients with sporadic keloids and explore potential therapeutic targets of keloids at the molecular level. METHODS: High-throughput sequencing data were obtained from normal skin tissue of patients with a family history of keloids (FN group) and normal skin tissue from sporadic patients (N group). Bioinformatics analysis was employed to identify hub genes. Promising hub genes were identified using RT-qPCR, immunohistochemistry and immunofluorescence assays, and Western blotting. GO and KEGG pathway enrichment analysis was performed to determine the main functions between the two groups. RESULTS: Patients with a family history of keloids had more severe clinical symptoms (Ρ = -0.749, P < 0.001). The expression of IL-4 and CCR7 was significantly different between patients with a family history of keloids and those with sporadic keloids. The high expression of IL-4 and the low expression of CCR7 in the FN group may be of key importance in explaining why keloids run in families (P < 0.05). CONCLUSION: Having a family history of keloids is a risk factor for increased severity of keloids. IL-4 and CCR7 play an important role in the development of keloids in patients with a family history of the condition and may represent new targets for the treatment of keloids.

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

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.

Immune-related gene expression in skin, inflamed and keloid tissue from patients with keloids.

Keloids are a tumor-like fibroproliferative skin disease that could cause disfigurement and disability. The pathological mechanisms underlying this condition remain unclear, particularly the progression from normal healthy skin to inflammatory skin tissue, then keloid. In the present study, three immune-related gene expression profiling datasets, were obtained from normal skin tissue (N group), inflamed tissue (I group) and keloid tissue samples from patients with keloids (K group). This sample grouping represents the primary steps of keloid formation, from normal to inflammatory, and finally to keloid tissue. The expression levels of immune-related genes were analyzed, and the differentially expressed genes (DEGs) between the three groups were compared. Protein-protein interaction networks were established using Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were carried out to determine the main functions associated with the DEGs and keloid-associated pathways. The results identified hub genes in the N and I groups, including C-C motif chemokine receptor (CCR) 1, CCR7, CD40 ligand, C-X-C motif chemokine ligand 9, IL-6 and IL-10. The hub genes in the I and the K groups included IL-10, IL-6, IL-13 and CD86. The expression levels of these genes were verified using reverse transcription-quantitative PCR. The results demonstrated that IL-6 expression levels were significantly increased in the I group compared with the N group (P=0.0111). CCR7 levels significantly differed between all three groups (P<0.017). The results of GO analysis suggested that the hub genes in the I and N groups may be associated with 'regulation of lymphocyte activation' and 'T-cell activation'. Similar results were also observed between the I and K groups, which may play an important role in keloid initiation and formation. In conclusion, CCR7, IL-10 and IL-6 may be important in keloid initiation and formation. These findings provided insight into the pathogenesis of keloids and may help identify novel immune-related therapeutic targets for this condition.

Skin endothelial cell and microcirculation function study in recurred keloids patients after keloid surgery and radiotherapy.

BACKGROUND: Keloid is a type of benign tumor of the skin with abnormal proliferation of fibrous tissue. We sought to observe the changes in skin microcirculation and endothelial cell function around the recurred keloid and explore the skin microcirculation characters in recurred keloid patients. METHODS: Six patients with recurred keloid were treated with keloid surgery and radiotherapy for the second time. Microcirculation of recurred keloids and their surrounding normal skin tissue was observed with laser Doppler flowmeter before operation. Expression of vascular endothelial growth factor (VEGF), CD31, and HIF-1α were identified by several assay. RESULTS: The local blood flow of group RN was enhanced. The average strength of group N is 0.87. The average strength of group RN is 2.08. The expression of VEGF, CD31, and hypoxia inducible factor-1α (HIF-1α) protein in the keloid-recurred skin (RN) group was higher than the normal skin group via immunohistochemistry (IHC) and Western blotting analysis. The relative expression of VEGF and CD31 mRNA was significantly increased in RN group samples (P < .05). CONCLUSIONS: There are significant differences in the expression of VEGF, CD31, and HIF-1α in the recurred keloid skin after radiotherapy and normal skin. They may be used as potential biomarkers and targets for future research on keloid recurrence.