What question did this study set out to answer?

This study aims to profile lipid factors in lymphedema patients and assess their diagnostic value.

April 8, 2026Open Access

Proteins related to cholesterol metabolism were screened and identified in the serum of lymphedema patients

Key Points

This study aims to profile lipid factors in lymphedema patients and assess their diagnostic value.
Compared serum lipid profiles between lymphedema patients and normal controls.
Identified differentially expressed proteins (DEPs) related to lipid metabolism.
Used enzyme-linked immunosorbent assay (ELISA) to validate candidate proteins.
Employed ROC curve analysis to evaluate diagnostic potential.
Cholesterol metabolism pathway was significantly enriched in LE patients.
Beta-2-glycoprotein 1 (β2GPI) was significantly upregulated in the serum of LE patients.
ROC analysis showed β2GPI distinguished LE patients with an AUC of 0.873 for primary LE and 0.871 for secondary LE.
For primary LE, β2GPI had 80.0% sensitivity and 86.7% specificity; for secondary LE, both metrics were 86.7%.

Abstract

Currently, it remains unclear whether patients with lymphedema (LE) exhibit lipid metabolism disorders. This study aimed to profile serum lipid factors associated with LE and evaluate their clinical diagnostic value. Differentially expressed proteins (DEPs) were identified by comparing serum lipid profiles between LE patients and normal controls (NC). Bioinformatics analyses were subsequently conducted to identify lipid metabolism-related proteins in LE patients. Enzyme-linked immunosorbent assay (ELISA) and receiver operating characteristic (ROC) curve analysis were employed to validate and evaluate the diagnostic potential of candidate proteins. Enrichment analysis of DEPs revealed that the cholesterol metabolism pathway was prominently enriched in the serum of LE patients. Annotated proteins involved in this pathway included beta-2-glycoprotein 1 (β2GPI), apolipoprotein A-I (Apo-AI), apolipoprotein E (Apo-E), apolipoprotein C-III (ApoC-III), apolipoprotein B-100 (ApoB-100), phosphatidylcholine–sterol acyltransferase (LCAT), and phospholipid transfer protein (PLTP). Among these, β2GPI was confirmed to be significantly upregulated in the serum of LE patients by ELISA (p < 0.05). ROC analysis demonstrated that serum β2GPI effectively distinguished LE patients from controls, with AUCs of 0.873 (95% CI 0.749–0.998, p < 0.05) for primary LE (PLE) and 0.871 (95% CI 0.738–1.000, p < 0.05) for secondary LE (SLE). For PLE diagnosis, β2GPI exhibited 80.0% sensitivity and 86.7% specificity. For SLE diagnosis, it showed 86.7% for both sensitivity and specificity. Abnormal expression of cholesterol metabolism-related proteins was observed in the serum of LE patients. Among these, β2GPI was validated to be significantly upregulated, demonstrating its potential clinical diagnostic value.

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