Identification and Validation of Hub Genes for Predicting Treatment Targets and Immune Landscape in Rheumatoid

Xinling He1, Ji Yin1, Mingfang Yu1,2

  • 1The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 646000, China.

Abstract

Insights

This study identifies three key genes, CRTAM, CXCL13, and LRRC15, involved in rheumatoid arthritis (RA) pathogenesis. These findings offer potential new targets for RA diagnosis and treatment.

Area of Science:

  • Immunology
  • Genetics
  • Bioinformatics

Background:

  • Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial inflammation.
  • The precise pathophysiological mechanisms underlying RA remain incompletely understood.
  • Identifying novel therapeutic targets for RA is crucial.

Purpose of the Study:

  • To explore the underlying mechanisms of RA using bioinformatics analysis.
  • To identify potential therapeutic targets for RA.
  • To investigate the role of specific genes and immune cell infiltration in RA development.

Main Methods:

  • Downloaded and analyzed four microarray datasets (GSE77298, GSE55235, GSE12021, GSE55457) from the GEO database.
  • Utilized R software packages ('limma', 'sva') for differential gene expression analysis.
  • Performed Gene Ontology (GO), KEGG, and Gene Set Enrichment Analysis (GSEA) for functional annotation.
  • Screened hub genes using LASSO and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) analyses.
  • Validated hub gene expression in rat synovial tissues via qRT-PCR and Western blot.
  • Assessed immune cell infiltration using CIBERSORTx.

Main Results:

  • Identified CRTAM, CXCL13, and LRRC15 as potential hub genes in RA through machine learning and LASSO algorithms.
  • Confirmed the differential expression of these hub genes in RA.
  • Revealed that plasma cells, T follicular helper cells, M0 and M1 macrophages, and gamma delta T cells may play significant roles in RA development and progression.
  • Demonstrated associations between hub genes and infiltrating immune cells.

Conclusions:

  • CRTAM, CXCL13, and LRRC15 are identified as key genes potentially involved in the pathological development of RA.
  • These validated hub genes provide novel perspectives for RA diagnosis and treatment strategies.
  • Immune cell infiltration patterns offer insights into RA pathogenesis.

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