Translating molecular medicine into clinical tools: doomed to fail by neglecting basic preanalytical principles

Area of Science:

• Biochemistry
• Translational Medicine
• Clinical Diagnostics

Background:

• Matrix metalloproteinase 9 (MMP-9) is a key enzyme implicated in various physiological and pathological processes.
• Pseudoxanthoma elasticum (PXE) is a rare genetic disorder affecting connective tissue, with potential links to MMPs.
• Accurate measurement of circulating biomarkers is crucial for advancing translational medicine.

Purpose of the Study:

• To comment on a study measuring MMP-9 in pseudoxanthoma elasticum (PXE) patient serum.
• To highlight the challenges and limitations of using serum for MMP-9 quantification in translational research.
• To emphasize the need for appropriate sample selection in biomarker studies.

Main Methods:

• The commentary reviews a published study that measured MMP-9 concentrations in serum samples from PXE patients.
• It references comparative analyses of MMP-9 levels in serum versus plasma.
• The discussion points to the inherent limitations of serum as a sample matrix for MMP-9 determination.

Main Results:

• Serum measurements of MMP-9 in PXE patients were found to be potentially unreliable.
• Comparative studies indicate significantly higher MMP-9 levels in serum compared to plasma.
• This discrepancy is attributed to the release of MMP-9 from leukocytes and platelets during serum coagulation.

Conclusions:

• The use of serum for MMP-9 measurements in PXE patients presents a significant obstacle to effective translational medicine.
• Translational research requires careful consideration of sample matrices to ensure accurate biomarker quantification.
• Enhanced collaboration between basic researchers and clinicians is essential to prevent 'lost in translation' scenarios.