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Using Quantitative Proteomic Assessments and their Association with Long Term Healing Outcomes

ABSTRACT: Healing after Achilles tendon rupture (ATR) is protracted with high individual variation and unsatisfactory outcome. Biomarkers prognostic of healing are unknown while physical and mechanical factors are used for predicting long-term healing outcomes in clinics today. The present study was designed to investigate the proteomic profile of healing, identify potential biomarkers, and asess the association with the patient's long term outcomes after ATR. Using quantitative Mass Spectrometry (MS) analysis, 1423 proteins in healing and contralateral healthy Achilles tendon from 28 ATR patients were quantified. Comparing healing and healthy protein profiles, we identified 821 overlapping proteins. Further analysis revealed 390 up-regulated and 17 down-regulated proteins in healing compared to the healthy contralateral side,mainly related to extracellular matrix organization, inflammation, and reduced exocytosis and metabolic pathways. Our analysis based on clinical parameters, identified complement factor D (CFD) as the most reliable predictive biomarker of successful tendon healing.Our findings identidied identified prognostic biomarkers and potential therapeutic target for improving tendon or ligament injuries.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Tendon

SUBMITTER: JIMMY RODRIGUEZ

LAB HEAD: Junyu Chen

PROVIDER: PXD029202 | Pride | 2022-05-25

REPOSITORIES: Pride

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Project description:Healing process after connective tissues (CT) injury is complex but important as CT are critical for human moving, and patient outcome of CT injured patients is protracted with high individual variation. Specific markers which could be used for healing prognosis will be great help to monitor patient outcome, and furtherly improve target treatment and patient recovery. Although several common factors like age, gender and body mass index (BMI) were reported to predict ATR healing outcome [references], more specific markers which can be used as predictors of patient outcome after ATR are still lacking. Several biomarkers have been reported to associate with tendon healing, and indicated their relationship with patient outcome(1-4). These results highlight the potential of protein expression detection and analysis for tendon study in general and healing outcome prognosis in particular. Collagen type I (Col1a1) is the main component of Achilles tendon and plays vital role in tendon healing via involving in collagen fibrils production among tendon fibroblasts(5). Higher production of Col1a1 is associated with faster tendon repair(6), previous study on animal model reported the increased Col1a1 synthesis can exert a positive effect on tendon healing[?]. Thus, functional proteins with high impact on Col1a1 can be used not only to improve tendon healing, also can be as targets for healing improvement and outcome prediction. The proteome file of Achilles tendon which is important to increase understanding of tendon healing and help to identify accurate outcome-related biomarkers is however lagged behind. The identification of proteomic profile of Achilles tendon is very much limited in number of proteins and sample size(7-9), and is even few on human. Recent improvement in proteomic assay based on mass spectrometry (MS) made it possible to assemble the proteomic landscape of human tissues(10, 11) with high quality and sensitivity. To characterize the proteomic components in human Achilles tendon, we utilized biopsies from ATR patients with both good and poor 1-year healing outcome. A validated platform including quantitative MS and clinical database was used to identify proteomic landscape and potential bio-predictors of clinical outcome. Our study may provide a more comprehensive landscape of proteins for human Achilles tendon, as well as specific biomarkers which can be used for long term outcome prognosis after ATR.

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Using Quantitative Proteomic Assessments and their Association with Long Term Healing Outcomes

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