Higher Growth Differentiation Factor 15 Levels Research Articles

Growth differentiation factor-15, a novel biomarker related with disease severity in patients with hypertrophic cardiomyopathy

BackgroundThe growth differentiation factor 15 (GDF-15) has been shown up-regulated in stress conditions and to have regulatory actions in myocyte hypertrophy. We hypothesized that GDF-15 could be related to disease severity and functional status in patients with hypertrophic cardiomyopathy (HCM). Methods and resultsWe performed a study which includes 102 consecutive outpatient HCM subjects, 73% males, aged 47.1±14.6years. A complete history and clinical examination was performed, including 12-lead electrocardiogram, echocardiography, symptom-limited treadmill exercise, 24-hour ECG-Holter monitoring, and magnetic resonance with Gadolinium. Several biomarkers, associated with myocardial remodeling and damage, were compared to GDF-15 levels. The assays were performed with commercial ELISAs or standardized methods when available. There was a significant association between GDF-15 levels and comorbidities, being higher in hypertension (p=0.001), diabetes (p=0.030), atrial fibrillation (p=0.012), dyspnea (p=0.020) and NYHA≥II functional class (p=0.037). GDF-15 levels were positively correlated with clinical variables (age, worse exercise capacity and mild renal dysfunction) and biomarkers of interstitial remodeling, such as metalloproteinase-2 (r: 0.40; p=0.009), N-terminal pro-B-type natriuretic peptide (r: 0.28; p=0.049), high-sensitivity troponin T (r: 0.30; p=0.003) and von Willebrand factor (r: 0.33; p=0.001). Multivariate analysis was assessed to estimate the involvement of these different factors in the GDF-15 levels, confirming the independent implication of severe dyspnea and functional status. ConclusionsThe present results show that higher levels of GDF-15 are associated to conditions of severe disease in HCM. Hence, GDF-15 is suggested as a novel marker related to the severity and could represent a further useful tool in monitoring functional capacity of HCM patients.

Growth differentiation factor 15: a prognostic marker for recurrence in colorectal cancer

Background:Growth differentiation factor 15 (GDF15) belongs to the transforming growth factor beta superfamily and has been associated with activation of the p53 pathway in human cancer. The aim of this study was to assess the prognostic value of GDF15 in patients with colorectal cancer (CRC).Methods:Immunohistochemistry and tissue microarrays were used to analyse GDF15 protein expression in 320 patients with CRC. In a subgroup of 60 patients, the level of GDF15 protein in plasma was also measured using a solid-phase proximity ligation assay.Results:Patients with CRC with moderate to high intensity of GDF15 immunostaining had a higher recurrence rate compared with patients with no or low intensity in all stages (stages I–III) (HR, 3.9; 95% CI, 1.16–13.15) and in stage III (HR, 10.32; 95% CI, 1.15–92.51). Patients with high plasma levels of GDF15 had statistically shorter time to recurrence (P=0.041) and reduced overall survival (P=0.002).Conclusion:Growth differentiation factor 15 serves as a negative prognostic marker in CRC. High expression of GDF15 in tumour tissue and high plasma levels correlate with an increased risk of recurrence and reduced overall survival.

High levels of GDF15 in thalassemia suppress expression of the iron regulatory protein hepcidin

In thalassemia, deficient globin-chain production during erythropoiesis results in anemia. Thalassemia may be further complicated by iron overload (frequently exacerbated by blood transfusion), which induces numerous endocrine diseases, hepatic cirrhosis, cardiac failure and even death. Accumulation of iron in the absence of blood transfusions may result from inappropriate suppression of the iron-regulating peptide hepcidin by an erythropoietic mechanism. To test this hypothesis, we examined erythroblast transcriptome profiles from 15 healthy, nonthalassemic donors. Growth differentiation factor 15 (GDF15), a member of the transforming growth factor-beta superfamily, showed increased expression and secretion during erythroblast maturation. Healthy volunteers had mean GDF15 serum concentrations of 450 +/- 50 pg/ml. In comparison, individuals with beta-thalassemia syndromes had elevated GDF15 serum levels (mean 66,000 +/- 9,600 pg/ml; range 4,800-248,000 pg/ml; P < 0.05) that were positively correlated with the levels of soluble transferrin receptor, erythropoietin and ferritin. Serum from thalassemia patients suppressed hepcidin mRNA expression in primary human hepatocytes, and depletion of GDF15 reversed hepcidin suppression. These results suggest that GDF15 overexpression arising from an expanded erythroid compartment contributes to iron overload in thalassemia syndromes by inhibiting hepcidin expression.