ITRAQ-based proteomics reveals potential markers and treatment pathways for acute Achilles tendon rupture

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BackgroundDue to its limited blood supply and irregular mechanical loading, the Achilles tendon is the most frequently ruptured tendon. Despite the rising incidence of acute Achilles tendon rupture (AATR), the optimal treatment remains controversial. Missed diagnoses and delayed treatments lead to poor outcomes and limited treatment options. This study aimed to identify potential biomarkers for diagnosing and developing therapies for AATR.MethodsWe employed the coupled isobaric tag for relative and absolute quantitation-liquid chromatography–electrospray ionization-tandem mass spectrometry approach to investigate protein expression in tissues from AATR patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to identify differentially expressed proteins (DEPs) between AATR patients and healthy individuals. A protein–protein interaction (PPI) network of DEPs was constructed using the Search Tool for the Retrieval of Interacting Genes. The screened hub genes were selectively verified by immunohistochemical staining.ResultsWe identified 410 DEPs between AATR patients and controls. The DEPs were significantly enriched in GO terms such as the extracellular region, extracellular region part, and defense response, as well as KEGG pathways, including complement and coagulation cascades, focal adhesion, and regulation of actin cytoskeleton. The main hub nodes in the PPI network comprised fibronectin 1 (FN1), major histocompatibility complex, class I, B (HLA-B), filamin A (FLNA), heat shock 27-kDa protein 1 (HSPB1), heat shock protein family A member 5 (HSPA5), apolipoprotein A4 (APOA4), and myosin IC (MYO1C). Although APOA4 and collagens I, II, and III were detectable in healthy tendons, immunohistochemical staining confirmed higher expression of these proteins in the acutely ruptured Achilles tendon.ConclusionsOur findings lay a foundation for further molecular studies of AATR. Inflammation and age-related degeneration may contribute to the pathogenesis of AATR. Moreover, the identified DEPs could be potential biomarkers for AATR diagnosis and treatment.