Skin Gene Expression Profiles in Systemic Sclerosis: From Clinical Stratification to Precision Medicine

Abstract

Systemic sclerosis, also known as scleroderma or SSc, is a condition characterized by significant heterogeneity in clinical presentation, disease progression, and response to treatment. Consequently, the design of clinical trials to successfully identify effective therapeutic interventions poses a major challenge. Recent advancements in skin molecular profiling technologies and stratification techniques have enabled the identification of patient subgroups that may be relevant for personalized treatment approaches. This narrative review aims at providing an overview of the current status of skin gene expression analysis using computational biology approaches and highlights the benefits of stratifying patients upon their skin gene signatures. Such stratification has the potential to lead toward a precision medicine approach in the management of SSc.

Keywords: SSc; fibrosis; scleroderma; skin gene expression; systemic sclerosis.

Figure 1

A representative network of skin gene expression profiles in systemic sclerosis, summarizing the most relevant genes and pathways resulting from literature revision. Global gene expression analysis (blue dot) revealed four intrinsic subsets (light blue dots) among patients with SSc: fibroproliferative, inflammatory, limited, and normal-like subsets. The present review focused on the inflammatory skin signature and the fibrotic expression profiles, highlighting their most relevant genes (yellow dots) and pathways (red dots). Moreover, gene expression and molecular signature in SSc may identify skin biomarkers (purple dots), genes, and pathways involved in the prediction of the trajectory of skin fibrosis and treatment response (green dot).