The circulating form of neprilysin is not a general biomarker for overall survival in treatment-naïve cancer patients.
Noemi PavoHenrike ArfstenAnna ChoGeorg GoliaschPhilipp E BartkoRaphael WurmClaudia FreitagHeinz GisslingerGabriela KornekGuido StrunkMarkus RadererChristoph ZielinskiMartin HülsmannPublished in: Scientific reports (2019)
The transmembrane zink-metalloendopeptidase neprilysin (NEP) is implicated in cardiovascular disease but also tumor biology. The aim of the study was to investigate the relationship of circulating NEP (cNEP) levels with established cardiovascular biomarkers and its effect on overall survival in an unselected cohort of treatment-naïve cancer patients. 555 consecutive cancer patients prior anticancer therapy were enrolled prospectively. NEP levels were determined alongside routine laboratory parameters, established cardiac biomarkers, i.e. NT-proBNP, hsTnT, MR-proANP, MR-proADM, CT-proET-1 and Copeptin, and inflammatory parameters, i.e. CRP, IL-6 and SAA, in venous plasma samples. All-cause mortality was the primary endpoint. cNEP levels of 276 pg/ml (IQR: 0-5981) displayed a weak inverse correlation with age [r = -0.12, p = 0.023] and inflammatory status [r = -0.14, p = 0.007 CRP; r = -0.20, p < 0.001 IL-6 and r = -0.18, p < 0.001 SAA]. cNEP was comparable between different tumor entities and stages and not related to functional parameters of other organ systems as kidney, liver or especially the heart. Moreover, cNEP was not associated with overall survival in the total cohort [adj.HR for ln (cNEP) 1.00, 95% CI: 0.94-1.06, p = 0.887] but in myelodysplatic malignancies [adj.HR for ln (cNEP) 1.27, 95% CI: 1.01-1.61, p = 0.044]. In conclusion, cNEP lacks association with outcome but for myelodysplastic disease. cNEP shows no correlation with established cardiovascular biomarkers related to prognosis, thereby holding a limited potential as a biomarker in cardio-oncology.
Keyphrases
- cardiovascular disease
- contrast enhanced
- oxidative stress
- magnetic resonance
- type diabetes
- heart failure
- free survival
- acute myeloid leukemia
- metabolic syndrome
- magnetic resonance imaging
- clinical practice
- atrial fibrillation
- risk assessment
- replacement therapy
- dual energy
- cardiovascular events
- cardiovascular risk factors
- chemotherapy induced