Reactome Pathway Analysis From Whole-Blood Transcriptome Reveals Unique Characteristics of Systemic Sclerosis Patients at the Preclinical Stage

Authors

Chiara Bellocchi
Xuan Wang
Marka A Lyons
Maurizio Marchini
Maurizio Lorini
Vincenzo Carbonelli
Nicola Montano
Shervin Assassi
Lorenzo Beretta

Publication Date

1-1-2023

Journal

Frontiers in Immunology

Abstract

OBJECTIVE: This study aims to characterize differential expressed pathways (DEP) in subjects with preclinical systemic sclerosis (PreSSc) characterized uniquely by Raynaud phenomenon, specific autoantibodies, and/or capillaroscopy positive for scleroderma pattern.

METHODS: Whole-blood samples from 33 PreSSc with clinical prospective data (baseline and after 4 years of follow-up) and 16 matched healthy controls (HC) were analyzed for global gene expression transcriptome analysis via RNA sequencing. Functional Analysis of Individual Microarray Expression method annotated Reactome individualized pathways. ANOVA analysis identified DEP whose predictive capability were tested in logistic regression models after extensive internal validation.

RESULTS: At 4 years, 42.4% subjects progressed (evolving PreSSc), while the others kept stable PreSSc clinical features (stable PreSSc). At baseline, out of 831 pathways, 541 DEP were significant at a false discovery rate

CONCLUSION: PreSSc had distinguished Reactome pathway signatures compared to HC. Progression to definite SSc was characterized by a shift in biological fingertips. Calcium-related events promoting endothelial damage and vasculopathy may be relevant to disease progression.

Keywords

systemic sclerosis, preclinical systemic sclerosis, pathways, disease progression, gene expression

Comments

Supplementary Materials

PMID: 38022564