GDF-15 in solid vs non-solid treatment-naïve malignancies.
Adrenomedullin
/ blood
Aged
Breast Neoplasms
/ blood
C-Reactive Protein
/ metabolism
Cause of Death
Endothelin-1
/ blood
Female
Gastrointestinal Neoplasms
/ blood
Glycopeptides
Growth Differentiation Factor 15
/ blood
Humans
Interleukin-6
/ blood
Lung Neoplasms
/ blood
Male
Middle Aged
Mortality
Myelodysplastic Syndromes
/ blood
Myeloproliferative Disorders
/ blood
Natriuretic Peptide, Brain
/ blood
Neoplasm Metastasis
Neoplasms
/ blood
Peptide Fragments
/ blood
Prognosis
Proportional Hazards Models
Prospective Studies
Protein Precursors
/ blood
Serum Amyloid A Protein
/ metabolism
Troponin T
/ blood
GDF-15
biomarker
cancer
inflammation
prognosis
Journal
European journal of clinical investigation
ISSN: 1365-2362
Titre abrégé: Eur J Clin Invest
Pays: England
ID NLM: 0245331
Informations de publication
Date de publication:
Nov 2019
Nov 2019
Historique:
received:
07
10
2018
revised:
30
07
2019
accepted:
25
08
2019
pubmed:
30
8
2019
medline:
10
6
2020
entrez:
30
8
2019
Statut:
ppublish
Résumé
GDF-15 is an established cardiovascular risk marker but is equally implicated in tumour biology. Elevated levels of GDF-15 have indeed been observed in distinct tumour entities. This study aimed to explore the relation of GDF-15 to other cardiac biomarkers and the general association of GDF-15 on prognosis in an unselected cohort of treatment-naïve cancer patients. We prospectively enrolled 555 consecutive patients at time of diagnosis of malignant disease prior receiving anticancer therapy. Plasma GDF-15 concentrations were determined alongside other cardiac and routine laboratory markers. All-cause mortality was defined as primary endpoint. GDF-15 levels were 338 ng/L (IQR:205-534) for the total cohort, and values were comparable for different tumour entities except breast cancer. Metastatic disease was characterized by higher plasma GDF-15 [435 ng/L (IQR:279-614) vs 266 ng/L (IQR:175-427), P < .001]. GDF-15 correlated positively with inflammatory status reflected by CRP, SAA and IL-6 [r = .31, P < .001, r = .23, P < .001 and r = .14, P = .002] and cardiac biomarkers as NT-proBNP, hsTnT, MR-proADM and CT-proET-1 [r = .46; r = .46; r = .59 and r = .50; P < .001 for all]. GDF-15 was significantly associated with all-cause mortality after multivariate adjustment [adj.HR for ln(GDF-15) 1.78, 95%CI:1.47-2.16, P < .001]. There was a significant interaction between solid and haematological malignancies with loss of association of GDF-15 with outcome in myelodysplastic and myeloproliferative disease. Elevated plasma GDF-15 is associated with progressing disease severity and poor prognosis in solid tumours of treatment-naïve cancer patients. GDF-15 increase is accompanied by worsening systemic inflammation and a subclinical functional impairment of different organs including the heart. GDF-15 represents a promising target for our pathophysiologic understanding in cardio-oncology linking conditions of both cardiac and neoplastic disease.
Identifiants
pubmed: 31463975
doi: 10.1111/eci.13168
pmc: PMC6899906
doi:
Substances chimiques
C-terminal proendothelin-1
0
Endothelin-1
0
GDF15 protein, human
0
Glycopeptides
0
Growth Differentiation Factor 15
0
IL6 protein, human
0
Interleukin-6
0
Peptide Fragments
0
Protein Precursors
0
Serum Amyloid A Protein
0
Troponin T
0
copeptins
0
mid-regional pro-adrenomedullin, human
0
pro-brain natriuretic peptide (1-76)
0
Natriuretic Peptide, Brain
114471-18-0
Adrenomedullin
148498-78-6
C-Reactive Protein
9007-41-4
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13168Subventions
Organisme : Thermo Fisher Scientific
ID : This study was supported by an unrestricted grant
Informations de copyright
© 2019 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.
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