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Background: Lymphedema (LE) is a chronic disease that can lead to disability. Currently, the pathogenesis of LE remains unclear, and there is a lack of serum proteins applicable for diagnosis in clinical practice. This study aimed to screen and identify the differentially expressed proteins in serum samples of limb lymphedema and normal subjects and to further explore their value in the diagnosis of LE.
Methods: Nano-flow reverse phase liquid chromatography-tandem mass spectrometry (Nano RPLC-MS/MS) was used to establish the serum protein profiles of primary lymphedema (PLE), secondary lymphedema (SLE), and normal controls (NC). Differentially expressed serum proteins were screened and identified. Subsequently, enrichment analysis was performed for proteins that were upregulated in the LE group compared to the NC group. The target protein was validated by western blot (WB) and enzyme-linked immunosorbent assay (ELISA). Both the receiver operating characteristic (ROC) curve and Spearman’s correlation test were employed to evaluate the diagnostic performance of the protein and its relationship with disease severity.
Results: A total of 362 serum proteins were identified, among which 241 proteins were differentially expressed among PLE, SLE, and NC subjects (p < 0.05, fold change > 1.2). The enriched pathway correlated with cornified envelope formation was selected for further analysis. Cathepsin D (CTSD), a target protein involved in the selected pathway, was found to be up-regulated in the serum of PLE and SLE patients compared to NC. The AUCs of CTSD were 0.849 and 0.880 for patients with PLE and SLE, respectively. There was a significant positive correlation between the levels of serum CTSD and disease severity in the PLE group.
Conclusions: Proteomic analysis found that the levels of serum proteins related to cornified envelope formation were elevated in patients with limb lymphedema. Serum CTSD was highly expressed in patients with limb lymphedema and showed good diagnostic value.
DOI: 10.7754/Clin.Lab.2023.221029
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