Osteopontin: a novel predictor of survival in patients with systemic light-chain amyloidosis

Amyloid. 2014 Sep;21(3):202-10. doi: 10.3109/13506129.2014.940457. Epub 2014 Jul 9.

Abstract

Background: Troponin-T (cTnT) and NT-proBNP provide prognostic information in light-chain amyloidosis (AL). Thus, these biomarkers are widely used in clinical routine for risk stratification. Recently, plasma level of osteopontin (OPN), a secreted phosphoglycoprotein expressed by a variety of cell types, has been reported as a risk predictor in various cardiovascular diseases.

Methods: OPN was determined retrospectively in 150 consecutive patients newly diagnosed with AL amyloidosis. All patients were evaluated according to a routine protocol including electrocardiography, echocardiography and laboratory testing.

Results: Mean OPN was 591 ± 37 ng/mL. Cardiac involvement was established in 83 (55.3%). Median OPN plasma level were associated with number of organs involved, renal function, eligibility for high-dose melphalan chemotherapy and autologous stem cell transplantation, and severity of cardiac amyloidosis. Median follow-up was 19.2 months. 1-year all-cause-survival was 83.4%. The cut-offs discriminating 1-year all-cause-mortality for NT-proBNP, troponin T, and OPN were 2544 ng/L, 0.035 µg/L, and 426.8 ng/mL, respectively. Outcome was worse in patients with biomarkers above the individual ROC derived cut-off. A significant improvement of survival was observed in patients with cTNT >0.035 µg/L or NT-proBNP >2544 ng/L and OPN below ROC-derived cut-off of 426.8 ng/mL as compared to patients with OPN above 426.8 ng/L. No further discrimination was achieved by OPN in the cohorts of low troponin T or low NT-proBNP, respectively. Separate multivariate models identified OPN (cut-off 426.8 ng/mL) and troponin T (cut-off 0.035 µg/L) as independent predictors of all-cause-mortality.

Conclusions: These data demonstrated that OPN appears to be a valuable marker in the clinical routine for evaluation of patients with AL amyloidosis, especially if it is used in combination with cTNT and/or NT-proBNP.

Keywords: Amyloid; biomarker; natriuretic peptide; osteopontin; survival; troponin T.

MeSH terms

  • Aged
  • Amyloidosis / blood
  • Amyloidosis / complications
  • Amyloidosis / diagnosis*
  • Amyloidosis / therapy
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Biomarkers / blood
  • Cardiomyopathies / blood
  • Cardiomyopathies / complications
  • Cardiomyopathies / diagnosis*
  • Cardiomyopathies / therapy
  • Female
  • Gene Expression
  • Humans
  • Immunoglobulin Light Chains / blood
  • Immunoglobulin Light Chains / genetics
  • Immunoglobulin Light-chain Amyloidosis
  • Male
  • Melphalan / therapeutic use
  • Middle Aged
  • Natriuretic Peptide, Brain / blood*
  • Natriuretic Peptide, Brain / genetics
  • Osteopontin / blood*
  • Osteopontin / genetics
  • Peptide Fragments / blood*
  • Peptide Fragments / genetics
  • Prognosis
  • ROC Curve
  • Retrospective Studies
  • Stem Cell Transplantation
  • Survival Analysis
  • Transplantation, Autologous
  • Troponin T / blood*
  • Troponin T / genetics

Substances

  • Antineoplastic Agents, Alkylating
  • Biomarkers
  • Immunoglobulin Light Chains
  • Peptide Fragments
  • Troponin T
  • pro-brain natriuretic peptide (1-76)
  • Osteopontin
  • Natriuretic Peptide, Brain
  • Melphalan