Clinical Significance of Serum Collagen Type IV and Procollagen Type III N-Peptide Levels in Diagnosis and Differential Diagnosis of Lymphedema

Lymphat Res Biol. 2023 Feb;21(1):8-14. doi: 10.1089/lrb.2021.0076. Epub 2022 Jun 10.


Background: Lymphatic endothelial cells production or modification were closely related to the extracellular matrix (ECM) molecules. The serum hyaluronic acid (HA), laminin (LN), procollagen type III N-peptide (PIIINP), and collagen type IV (CGIV) levels were researched to explore the clinical significance of serum ECM proteins in the diagnosis and differentiation of lymphedema. Methods: Fifty-five patients were enrolled. They were divided into primary lymphedema (PLE), secondary lymphedema (SLE), and venous edema (VE) groups. Twenty-two healthy controls were also recruited as normal control (NC). Serum HA, LN, PIIINP, and CGIV levels of all subjects were assessed using chemiluminescence immunoassay. Statistical analysis and receiver operating characteristic (ROC) curves were used to data analysis. Results: The serum levels of CGIV were significantly decreased in both PLE and SLE groups compared with those in the NC group. Reduced serum CGIV levels were associated with the severity of lymphedema. The serum levels of CGIV and PIIINP were identified decreased in both PLE and SLE groups compared with those in the VE group. However, the levels of serum HA and LN were not observed significantly changed in both PLE and SLE groups than those in NC or VE group. Furthermore, ROC curve indicated that serum CGIV and PIIINP were capable of providing good diagnostic and differential diagnostic efficacy at the most appropriate cutoff point value. Conclusion: The serum levels of CGIV may have clinical significance in the diagnosis of lymphedema. CGIV and PIIINP may play a role in the differentiation of lymphedema from VE.

Keywords: collagen type IV; lymphedema; procollagen type III N-peptide; serum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Clinical Relevance
  • Collagen Type III
  • Collagen Type IV
  • Diagnosis, Differential
  • Endothelial Cells
  • Humans
  • Lupus Erythematosus, Systemic*
  • Lymphedema*


  • Collagen Type IV
  • Collagen Type III
  • Biomarkers