Evidence mapPaperPMID 40977679Full record

ArticleFrontiers in immunology2025

Identification of crosstalk genes and diagnostic biomarkers in systemic sclerosis associated sarcopenia through integrative analysis and machine learning.

Yanfang Wu, Yunfeng Dai, Fei Gao, Haiping Xie, Shuyao Pan, Juanjuan He, Jianwen Liu, He Lin, Zhihan Chen, Junping Wen

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Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Yanfang Wu *Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.
Yunfeng Dai *Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.
Fei Gao *Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.
Haiping Xie *Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.
Shuyao Pan *Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.
Juanjuan HeShengli Clinical Medical College of Fujian Medical University, Fuzhou, China.
Jianwen LiuShengli Clinical Medical College of Fujian Medical University, Fuzhou, China.
He LinShengli Clinical Medical College of Fujian Medical University, Fuzhou, China.
Zhihan ChenShengli Clinical Medical College of Fujian Medical University, Fuzhou, China.
Junping WenShengli Clinical Medical College of Fujian Medical University, Fuzhou, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Sarcopenia associated with systemic sclerosis (SSc) significantly compromises patient prognosis and quality of life. However, reliable diagnostic biomarkers remain lacking. This study aimed to identify molecular markers for early detection using integrative computational approaches. Methods: An integrated analysis based on the Gene Expression Omnibus (GEO) database was performed. Crosstalk genes (CGs) were identified using least absolute shrinkage and selection operator (LASSO) regularization, ensemble decision trees, and support vector machine-based feature selection. Machine learning algorithms were employed to construct a predictive scoring model and to assess the diagnostic value of key biomarkers. Hub mRNAs were validated using quantitative polymerase chain reaction (qPCR). Immune cell infiltration profiles and functional correlations were also examined. Results: Five key CGs-NOX4, STC2, NEK6, IGSF10, and EMX2-were identified as molecular links between SSc and sarcopenia. A predictive model incorporating NOX4 and NEK6 was developed, and a diagnostic threshold was established. PCR validation confirmed the differential expression of NOX4 and NEK6 in both SSc and SSc-associated sarcopenia, demonstrating high predictive accuracy. Furthermore, the combined NOX4-NEK6 model exhibited a superior area under the curve (AUC) compared to either gene alone. Immune infiltration analysis revealed significant correlations between CGs and multiple immune cell populations. Conclusion: This study proposes NOX4 and NEK6 as novel biomarkers, offering a non-invasive strategy for the early detection of SSc-associated sarcopenia. This study also reveals a shared immune-dysregulation node linking SSc and sarcopenia, positions these crosstalk genes as multi-disease prevention targets, and paves the way for personalized immunotherapy and rapid bench-to-bedside translation.

Indexed as

Machine LearningSarcopeniaScleroderma, SystemicBiomarkersComputational BiologyGene Expression ProfilingGene Regulatory NetworksHumansNADPH Oxidase 4NIMA-Related KinasesBiomarkersNADPH Oxidase 4NIMA-Related Kinasesbiomarkerimmune infiltrationmachine learningNEK6NOX4sarcopeniasystemic sclerosis

Identifiers

PMID40977679
PMCPMC12446289

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.