Discovery of Biomarkers Related to Symptoms and Treatment Response in Atopic Dermatitis: Finding New Indicators from Patient Skin to Advance Personalized Medicine
Science of the Month - September 2025
Nat Commun.
Fukushima-Nomura A, Kawasaki H, Yashiro K, Obata S, Tanese K, Ebihara T et al.
Atopic dermatitis (AD) is characterized by significant diversity in symptoms and individual differences in treatment response, and the full picture of its molecular basis has not been sufficiently elucidated. In this study, we conducted a large-scale study collecting 951 skin tissue samples (1 mm in diameter) from 156 patients and examined RNA-seq data through comprehensive analysis using unsupervised machine learning. Through this method, we succeeded in extracting gene groups co-expressed in patient skin. The extracted gene groups included not only those previously known to be related to the skin barrier and Type 2, Type 17, and Type 1 inflammation, but also extracellular matrix-related and immediate-early gene groups that have not been previously reported. More importantly, these gene groups were closely related to clinical symptoms such as erythema and lichenification, as well as the treatment responsiveness to the molecular targeted drug dupilumab. In particular, persistent expression of Type 17 inflammation-related and immediate-early gene groups was observed in treatment-resistant cases, suggesting a molecular basis that influences treatment efficacy. By comprehensively capturing skin gene expression patterns, this study presented new molecular signatures that can explain the diverse clinical presentations of AD. This marks a significant step toward the realization of personalized medicine.
(Ayano Nomura (Fukushima), Department of Dermatology)