# CLEC4E as a molecular biomarker in systemic lupus erythematosus: integrating bioinformatics and clinical data to assess its prognostic value

**Authors:** Xiaoxia Ma, Huan Zhang, Jiana Li

PMC · DOI: 10.3389/fimmu.2025.1617878 · 2025-09-30

## TL;DR

This study identifies CLEC4E as a potential biomarker for diagnosing and predicting the progression of systemic lupus erythematosus using bioinformatics and clinical data.

## Contribution

The novel contribution is the identification of CLEC4E as a prognostic and diagnostic biomarker for SLE through integrated bioinformatics and clinical validation.

## Key findings

- CLEC4E expression is significantly higher in SLE patients compared to healthy controls.
- CLEC4E is an independent predictor of SLE disease activity and is associated with worse prognosis.
- Combining CLEC4E with other biomarkers improves diagnostic accuracy (AUC = 0.9407).

## Abstract

This study explores the prognostic value of the CLEC4E gene in systemic lupus erythematosus (SLE) through bioinformatics analysis and evaluates its role in disease diagnosis and progression.

Gene expression datasets related to SLE (GSE17755, GSE50772, and GSE61635) were obtained from the GEO (Gene Expression Omnibus) database. Intersection analysis was performed using the Jvenn tool with a screening threshold of |log2FC| > 1 and P< 0.05 to identify differentially expressed genes (DEGs). The resulting DEGs were then cross-referenced with immune-related genes in the GeneCards database (relevance score > 8) to further prioritize candidates with immunological relevance. Peripheral blood from 360 SLE patients and 360 healthy controls was collected for CLEC4E expression analysis via RT-qPCR. Disease activity was evaluated using the SLEDAI score, and patients were grouped accordingly. Pearson and Spearman correlation analysis to investigate the relationship between CLEC4E and immune indicators. Logistic regression and ROC analyses were conducted to assess diagnostic and prognostic value. Kaplan-Meier analysis evaluated survival outcomes.

Bioinformatics analysis identified six SLE-related DEGs, namely ISG15, HERC5, TNFAIP6, IFIT3, OASL, and CLEC4E. Further intersection with immune-related genes from the GeneCards database (relevance score > 8) ultimately highlighted CLEC4E as the key gene for clinical validation. The expression level of CLEC4E was significantly higher in SLE patients compared with healthy controls. ROC analysis showed good diagnostic performance (AUC = 0.7744). CLEC4E expression was higher in active SLE, and multivariate analysis identified CLEC4E, C3, C4, ANA, and anti-dsDNA as independent predictors of disease activity. CLEC4E demonstrated moderate diagnostic value for distinguishing active from inactive disease (AUC = 0.6360). Higher CLEC4E expression was associated with worse prognosis (P = 0.0002). The combined diagnostic performance with other biomarkers (C3, C4, ANA, anti-dsDNA) showed a remarkable AUC of 0.9407.

CLEC4E is a potential biomarker for SLE diagnosis, disease activity assessment, and prognosis evaluation.

## Linked entities

- **Genes:** CLEC4E (C-type lectin domain family 4 member E) [NCBI Gene 26253], ISG15 (ISG15 ubiquitin like modifier) [NCBI Gene 9636], HERC5 (HECT and RLD domain containing E3 ubiquitin protein ligase 5) [NCBI Gene 51191], TNFAIP6 (TNF alpha induced protein 6) [NCBI Gene 7130], IFIT3 (interferon induced protein with tetratricopeptide repeats 3) [NCBI Gene 3437], OASL (2'-5'-oligoadenylate synthetase like) [NCBI Gene 8638]
- **Diseases:** systemic lupus erythematosus (MONDO:0007915), SLE (MONDO:0007915)

## Full-text entities

- **Genes:** IFIT3 (interferon induced protein with tetratricopeptide repeats 3) [NCBI Gene 3437] {aka CIG-49, GARG-49, IFI60, IFIT4, IRG2, ISG60}, ISG15 (ISG15 ubiquitin like modifier) [NCBI Gene 9636] {aka G1P2, IFI15, IMD38, IP17, UCRP, hUCRP}, OASL (2'-5'-oligoadenylate synthetase like) [NCBI Gene 8638] {aka OASL1, OASLd, TRIP-14, TRIP14, p59 OASL, p59-OASL}, HERC5 (HECT and RLD domain containing E3 ubiquitin protein ligase 5) [NCBI Gene 51191] {aka CEB1, CEBP1}, TNFAIP6 (TNF alpha induced protein 6) [NCBI Gene 7130] {aka TSG-6, TSG6}, CLEC4E (C-type lectin domain family 4 member E) [NCBI Gene 26253] {aka CLECSF9, MINCLE}
- **Diseases:** SLE (MESH:D008180)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12518280/full.md

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Source: https://tomesphere.com/paper/PMC12518280