Dataset Information

Elevated NF-κB/SHh/GLI1 Signature Denotes a Worse Prognosis and Represent a Novel Potential Therapeutic Target in Advanced Prostate Cancer.

ABSTRACT: Prostate cancer (PCa) is the second most frequent cancer in men worldwide. NF-κB seems to play a key role in cell survival, proliferation and invasion, sustaining the heterogeneous multifocal nature of PCa. In recent years, the Hedgehog (Hh) signaling pathway has attracted attention as a therapeutic target due to its implication in tumorigenesis and metastasis in several types of cancer, including PCa. Although it is well-known that Sonic Hedgehog (SHh) is a transcriptional target of NF-κB(p65), and that GLI1 is the effector of this crosstalk, the precise role played by this axis in PCa is still not completely clear. Here, we set out to explore the correlation between NF-κB activation and SHh pathways in PCa, investigating if the interplay between NF-κB(p65) and SHh-GLI1 in advanced PCa could be a prospective therapeutic target. Our findings demonstrate that a NF-κB-SHh-GLI1 gene signature is enriched in PCa patients featuring a higher Gleason score. Moreover, elevated levels of this signature are associated with worse prognosis, thus suggesting that this axis could provide a route to treat aggressive PCa.

SUBMITTER: Vecchiotti D

PROVIDER: S-EPMC9266159 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Elevated NF-κB/SHh/GLI1 Signature Denotes a Worse Prognosis and Represent a Novel Potential Therapeutic Target in Advanced Prostate Cancer.

Vecchiotti Davide D Verzella Daniela D Di Vito Nolfi Mauro M D'Andrea Daniel D Flati Irene I Di Francesco Barbara B Cornice Jessica J Alesse Edoardo E Capece Daria D Zazzeroni Francesca F

Cells 20220705 13

Prostate cancer (PCa) is the second most frequent cancer in men worldwide. NF-κB seems to play a key role in cell survival, proliferation and invasion, sustaining the heterogeneous multifocal nature of PCa. In recent years, the Hedgehog (Hh) signaling pathway has attracted attention as a therapeutic target due to its implication in tumorigenesis and metastasis in several types of cancer, including PCa. Although it is well-known that Sonic Hedgehog (SHh) is a transcriptional target of NF-κB(p65), ...[more]

PMID: 35805202

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Project description:AimsHeart failure (HF) is a progressive condition that is becoming more prevalent in the ageing population. Pulmonary hypertension is a common complicating factor in HF and negatively impacts survival. Plasma biomarkers are a potential method for determining the prognosis of patients with left heart failure with pulmonary hypertension (LHF-PH). We aimed to analyse the prognostic capability of 33 proteins related to, among other pathways, inflammation, coagulation, and Wnt signalling in LHF-PH.MethodsPlasma levels of 33 proteins were analysed using proximity extension assay from the plasma of 20 controls and 67 LHF-PH patients, whereof 19 underwent heart transplantation (HT). Haemodynamics in the patients were assessed using right heart catheterization.ResultsEleven proteins had elevated plasma levels in LHF-PH compared with controls (P < 0.01), which decreased towards the controls' levels after HT (P < 0.01). Survival analysis of these proteins showed that elevated plasma levels of growth hormone, programmed cell death 1 ligand 2, tissue factor pathway inhibitor 2, and Wnt inhibitory factor 1 (WIF-1) were associated with worse transplantation-free survival in LHF-PH (P < 0.05). When adjusted for age, sex and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels using multivariable cox regressions, only WIF-1 remained prognostic [hazard ratio (95% confidence interval)] [1.013 (1.001-1.024)]. WIF-1 levels in LHF-PH patients also correlated with the mean right atrial pressure (rs = 0.42; P < 0.01), stroke volume index (rs = 0.41; P < 0.01), cardiac index (rs = -0.42; P < 0.01), left ventricular stroke work index (rs = -0.41; P < 0.01), and NT-proBNP (rs = 0.63; P < 0.01).ConclusionsThe present study demonstrated that LHF-PH patients have higher plasma WIF-1 levels than healthy controls, suggesting that plasma WIF-1 may be a potential future prognostic biomarker in LHF-PH. Its prognostic capability could be further refined by including it in a multi-marker panel. Further studies are needed to establish the potential role of WIF-1 in LHF-PH pathophysiology in larger cohorts to determine its clinical applicability.

Dataset Information

Elevated NF-κB/SHh/GLI1 Signature Denotes a Worse Prognosis and Represent a Novel Potential Therapeutic Target in Advanced Prostate Cancer.

Publications

Elevated NF-κB/SHh/GLI1 Signature Denotes a Worse Prognosis and Represent a Novel Potential Therapeutic Target in Advanced Prostate Cancer.

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