Serum Cathepsin D was Elevated in Patients with Limb Lymphedema
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Updated: Jul 23, 2025

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Published on: January 12, 2017
Insights
This study identified elevated serum proteins, including Cathepsin D (CTSD), in lymphedema patients. CTSD shows promise as a diagnostic biomarker for lymphedema, correlating with disease severity.
Area of Science:
- Proteomics
- Biomarker Discovery
- Clinical Diagnostics
Background:
- Lymphedema (LE) is a chronic, disabling condition with unclear pathogenesis.
- Current diagnostic methods lack specific serum protein biomarkers.
- This study aimed to identify serum proteins for LE diagnosis.
Purpose of the Study:
- To screen and identify differentially expressed serum proteins in limb lymphedema.
- To evaluate the diagnostic value of identified proteins for lymphedema.
- To explore the relationship between protein levels and disease severity.
Main Methods:
- Serum samples from primary lymphedema (PLE), secondary lymphedema (SLE), and normal controls (NC) were analyzed using Nano RPLC-MS/MS.
- Differentially expressed proteins were identified, and pathway enrichment analysis was performed.
- Cathepsin D (CTSD) was validated using Western blot and ELISA, with diagnostic performance assessed by ROC curves.
Main Results:
- 362 serum proteins were identified, with 241 differentially expressed between LE and NC groups.
- Cathepsin D (CTSD) was significantly upregulated in PLE and SLE patients.
- CTSD demonstrated high diagnostic accuracy (AUCs 0.849 for PLE, 0.880 for SLE) and correlated positively with disease severity in PLE.
Conclusions:
- Proteomic analysis revealed elevated serum proteins associated with cornified envelope formation in lymphedema.
- Serum CTSD is highly expressed in lymphedema patients.
- CTSD exhibits significant potential as a diagnostic biomarker for limb lymphedema.
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.
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