Integrative Bioinformatics Identifies TTN as a Potential Diagnostic Marker for Rheumatoid Arthritis.

Authors

Yide Fang, Peihong Li, Zhujing Zhu, Zuoyuan Cao, Huanru Qu, Wei Wu, Liuqing Jing, Hao Li, Jinhai Xu, Bing Shu, Wen Mo

Published in

Current medicinal chemistry. Oct 06, 2026. Epub Oct 06, 2026.

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease with heterogeneous clinical manifestations, and its molecular mechanisms remain incompletely understood.
To identify core genes associated with RA and evaluate their diagnostic utility, with an emphasis on immune relevance and causality.
Differential expression analysis and weighted gene coexpression network analysis were used to prioritize hub genes. Functional enrichment and protein-protein interaction analyses supported biological interpretation. A nomogram and receiver operating characteristic analysis were used to evaluate diagnostic performance, and immune cell infiltration was analyzed to identify immune-associated core genes. The causal effect of titin on the risk of RA was estimated using genome-wide association study data and two-sample Mendelian randomization. Validation was conducted in independent public transcriptomic datasets and single-cell RNA sequencing (scRNA-seq) of synovial tissue.
Titin (TTN) was prioritized as an RA-associated core gene and demonstrated favorable diagnostic performance. TTN expression was consistently higher in RA than in controls across validation datasets. Public external validation datasets supported increased TTN expression in RA, and scRNA-seq analysis suggested enrichment of TTN expression in synovial T cells. Mendelian randomization supported a causal association between genetically predicted TTN and RA risk.
Collectively, evidence from bulk transcriptomics, immune cell infiltration profiling, single-cell localization, external validation, and genetic inference supports TTN as a previously underexplored candidate RA-associated biomarker with potential immune relevance. These findings extend current RA biomarker discovery by linking diagnostic performance with immune context and genetic support. Further mechanistic studies are needed to clarify whether TTN is involved in RA immunopathology or reflects inflammation-related tissue remodeling.
Integrative analyses identify TTN as a potential RA-associated diagnostic biomarker requiring further experimental and clinical validation. Further studies are needed to clarify its mechanistic role and clinical utility in RA.

PMID:
42864931
Bibliographic data and abstract were imported from PubMed on 13 Oct 2026.

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