Abstract

Tendinopathy is a complex multifaceted tendinopathy often associated with overuse and with its high prevalence resulting in significant health care costs. At present, the pathogenesis and effective treatment of tendinopathy are still not sufficiently elucidated. The purpose of this research is to intensely explore the genes, functional pathways, and immune infiltration characteristics of the occurrence and development of tendinopathy. The gene expression profile of GSE106292, GSE26051 and GSE167226 are downloaded from GEO (NCBI comprehensive gene expression database) and analyzed by WGCNA software bag using R software, GSE26051, GSE167226 data set is combined to screen the differential gene analysis. We subsequently performed gene enrichment analysis of Gene Ontology (GO) and "Kyoto Encyclopedia of Genes and Genomes" (KEGG), and immune cell infiltration analysis. By constructing the LASSO regression model, Support vector machine (SVM-REF) and Gaussian mixture model (GMMs) algorithms are used to screen, to identify early diagnostic genes. We have obtained a total of 171 DEGs through WGCNA analysis and differentially expressed genes (DEGs) screening. By GO and KEGG enrichment analysis, it is found that these dysregulated genes were related to mTOR, HIF-1, MAPK, NF-κB and VEGF signaling pathways. Immune infiltration analysis showed that M1 macrophages, activated mast cells and activated NK cells had infiltration significance. After analysis of THE LASSO SVM-REF and GMMs algorithms, we found that the gene MACROD1 may be a gene for early diagnosis. We identified the potential of tendon disease early diagnosis way and immune gene regulation MACROD1 key infiltration characteristics based on comprehensive bioinformatics analysis. These hub genes and functional pathways may as early biomarkers of tendon injuries and molecular therapy level target is used to guide drug and basic research.

Highlights

  • Tendinopathy is usually described as pathological changes in injured and diseased tendons, which in turn lead to limb pain and functional decline

  • After analysis of THE LASSO SVM-REF and Gaussian Mixture Model (GMM) algorithms, we found that the gene MACROD1 may be a gene for early diagnosis

  • We identified the potential of tendon disease early diagnosis way and immune gene regulation MACROD1 key infiltration characteristics based on comprehensive bioinformatics analysis

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Summary

Introduction

Tendinopathy is usually described as pathological changes in injured and diseased tendons, which in turn lead to limb pain and functional decline. It is characterized by abnormalities in the molecular structure, composition and cell matrix of the tendon [1]. Previous studies have suggested that the imbalance of normal homeostasis in tendon tissue, including immune cell infiltration, stromal cell dysfunction, cell apoptosis, oxidative stress, and stromal dysfunction, and these comprehensive conjunct factors lead to the early pathological changes of tendon [1]. The hub genes and pathways in the early stage of tendinopathy are blank studied, and understanding the key pathways that affect the regulation and dynamic homeostasis of the extracellular matrix in the early stage is critical for future targeted therapies of tendinopathy. More in-depth studies are urgently needed to elucidate the hub genes

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