Experimental Dermatology最新文献

Cutaneous squamous cell carcinoma (cSCC) is a common type of skin cancer, predominantly affecting elderly and immunosuppressed patients. Despite recent therapeutic advances, including the introduction of immune checkpoint inhibitors, outcomes for patients with metastatic or recurrent disease remain poor, underscoring the need for new therapeutic approaches and reliable biomarkers to identify patients at high risk of progression. In this context, receptor tyrosine kinase-like orphan receptor 1 (ROR1), previously associated with poor prognosis and targeted therapeutically in other malignancies, has not yet been investigated in cSCC. This study aimed to evaluate ROR1 expression in cSCC and investigate its potential role as a biomarker for tumour aggressiveness. ROR1 expression was analysed via immunofluorescence in a tissue microarray of 360 cSCC samples from a biobank cohort at the University Hospital Cologne. Fluorescence intensity was quantified and correlated with clinicopathologic features and patient outcomes. High ROR1 expression was detected in 42.5% of samples, predominantly localised at tumour invasive fronts. Elevated ROR1 levels were significantly associated with poor tumour differentiation (p < 0.001), lymph node metastasis (p = 0.007), and perineural invasion (p = 0.005). Although higher ROR1 expression correlated with worse progression-free and metastasis-free survival, these differences did not reach statistical significance. In conclusion, this study identifies ROR1 as a novel marker of aggressive cSCC, linked to poor differentiation, lymphatic spread and perineural invasion. ROR1 holds potential both as a prognostic biomarker and as a therapeutic target, encouraging future exploration of ROR1-directed therapies in advanced cSCC.

The epidermal differentiation complex (EDC) is a cluster of genes implicated in the control of the skin barrier. However, some EDC genes are also expressed at high levels in the human oesophagus. To determine whether the expression of EDC genes in the oesophagus is evolutionarily conserved, we performed comparative transcriptomic analyses of the skin and the oesophagus in humans, mice and chickens. Transcriptomes from public databases and newly generated RNA-sequencing data of the chicken oesophagus were compared. We found that the EDC of both mammals and birds contains genes that are predominantly expressed in the skin and others that are predominantly expressed in the oesophagus. Cornulin is strongly enriched in the oesophagus of humans and chickens. Similar to small proline-rich proteins in the human and murine oesophagus, an EDC protein rich in proline is predominantly expressed in the chicken oesophagus. Further oesophagus-enriched EDC genes are specific to phylogenetic lineages. This study indicates that the EDC plays evolutionarily ancient roles not only in the epidermis of the skin but also in the epithelium of the oesophagus. In line with the dual function of the EDC, dysregulation of EDC gene expression is associated with pathological changes in both stratified epithelia.

Vitiligo is a multifactorial chronic depigmentary disorder characterised by the loss of functional melanocytes. Its pathogenesis involves complex interactions among genetic predisposition, environmental factors, and autoimmune dysregulation. In recent years, extensive research has highlighted the critical role of epigenetic regulation in vitiligo development, including aberrant DNA methylation, dysregulated histone modifications, and non-coding RNA (ncRNA) expression disturbances. These abnormal epigenetic modifications contribute to disease progression by disrupting melanogenesis, promoting oxidative stress–induced melanocyte apoptosis, and driving autoimmune responses. From a translational perspective, specific epigenetic alterations show potential as diagnostic biomarkers, disease severity indicators, and therapeutic response monitors. Furthermore, epigenetic drugs, CRISPR/dCas9-based epigenetic editing, and targeted epigenetic reprogramming of tissue-resident memory T cells demonstrate promising clinical applications. This review systematically summarises the molecular mechanisms underlying epigenetic dysregulation in vitiligo pathogenesis and explores its translational implications, providing a theoretical foundation for advancing disease understanding and developing novel therapeutic strategies.

Inflammatory skin diseases are common and often difficult to differentiate. Ex vivo confocal laser scanning microscopy (EVCM) offers a rapid and promising approach. This study aimed to assess the diagnostic utility of EVCM in differentiating inflammatory dermatoses, particularly eczema, psoriasis and lichen planus, by comparing its performance with gold standard histopathology. Tissue samples of 110 patients presenting with inflammatory skin conditions were subjected to both EVCM and conventional histopathology. EVCM images were analysed by three blinded observers, with varying knowledge in histopathology and EVCM, utilising pattern analysis based on Ackermann's classification and single-cell analysis focusing on neutrophil (neutrophils) and eosinophil (eosinophils) granulocytes. Sensitivity and specificity were calculated using contingency tables. We used Cohen's Kappa coefficient and Firth's logistic regression models to evaluate the correlations between disease-associated histopathological features observed via EVCM and histopathology, as well as their impact on accurate histopathological diagnoses. Our findings demonstrate that EVCM provides rapid and insightful visualisation of characteristic features associated with inflammatory dermatological diseases. Diagnostic accuracy varied based on observer experience. The specialist proficient in both EVCM and histopathology achieved the highest accuracy rates for correctly diagnosing lichen planus (97.27%), psoriasis (95.45%) and eczema (92.73%). In conclusion EVCM emerges as a promising adjunct to histopathology, offering a swift and meaningful visualisation of inflammatory disease features. The integration of EVCM could significantly contribute to expediting diagnostic workflows and facilitating prompt, targeted therapeutic interventions. Further research and validation are warranted to establish EVCM's role in routine clinical practice.

Current prognostic evaluation in melanoma primarily relies on traditional histopathological and clinical staging evaluation; however, these conventional approaches exhibit limited accuracy and fail to account for individual patient heterogeneity. To address these limitations, we developed a machine learning-driven prognostic signature, with the objectives of identifying pivotal biomarkers and establishing a precision medicine framework for prognostic assessment in melanoma management. Bulk RNA-seq data of 636 melanoma patients were obtained from TCGA and GEO databases, followed by univariate Cox regression to identify prognosis-associated genes. Intersecting results across cohorts identified consistently prognostic genes. Heterogeneity of the selected genes was assessed between primary and metastatic melanoma using scRNA-seq data. The consensus prognosis-related signature was developed by systematically integrating 101 machine learning algorithms, with model performance rigorously evaluated through multidimensional metrics. Finally, molecular experiments validated the prognostic relevance of the model's hub genes, and the biological role of CUL2 was investigated in melanoma. 53 protective prognosis-related genes (PRGs) were identified in melanoma. Single-cell analysis revealed elevated PRGs activity in primary melanoma tissues compared to metastatic lesions. A 14-gene consensus prognosis-related signature was developed using LASSO and RSF algorithms. The model achieved a C-index of 0.908 in the TCGA-SKCM cohort and a mean C-index of 0.758 across four independent validation cohorts. Furthermore, the model outperformed 19 existing prognostic models across multiple cohorts. This study developed a 14-gene consensus prognosis-related signature validated for robust prognostic performance across cohorts. CUL2, identified as a pivotal protective biomarker in melanoma, demonstrates potent tumour-suppressive activity through significant inhibition of proliferation and migration potential.