GDF15/GFRAL Pathway as a Metabolic Signature for Cachexia in Patients with Cancer

Ahmed, Darakhshan Sohail; Isnard, Stéphane; Lin, John; Routy, Bertrand; Routy, Jean‐Pierre

doi:10.7150/jca.50376

Cited by 45 publications

(37 citation statements)

References 89 publications

(213 reference statements)

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“…29 Furthermore, similar to GDF-15, TNF is linked to cachexia, anorexia and muscle wasting. 28,[30][31][32][33] TNF-α exerts its cachexic effect through activation of death receptors TNF receptor 1 and 2 (TNFR1 and 2), which in turn leads to long-term overexpression of NF-κB dependent gene products and results in increased apoptosis, 34,35 and through interfering with neuropeptide Y release in the hypothalamus. 34,35 The upregulation of TNF-related proteins could thus partly explain why weight was consistently decreased, and NYHA class increased in upper compared to the lower quartiles of GDF-15 patients in both cohorts.…”

Section: Inflammatory Pathwaysmentioning

confidence: 99%

Pathophysiological pathways related to high plasma growth differentiation factor 15 concentrations in patients with heart failure

Ceelen

Voors

Tromp

et al. 2022

European J of Heart Fail

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Section: Inflammatory Pathwaysmentioning

confidence: 99%

Pathophysiological pathways related to high plasma growth differentiation factor 15 concentrations in patients with heart failure

Ceelen

Voors

Tromp

et al. 2022

European J of Heart Fail

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“…Finally, Growth Differentiation Factor 15 (GDF15), a stress-inducible cytokine, also has important implications in the context of ccRCC. It plays key roles in prenatal development, inflammation, regulation of cellular responses to stress signals, and tissue repair [ 41 , 42 ]. GDF-15 has been reported as a biomarker in several kinds of pathologies, including kidney disease [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Does the Urinary Proteome Reflect ccRCC Stage and Grade Progression?

et al. 2021

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Due its ability to provide a global snapshot of kidney physiology, urine has emerged as a highly promising, non-invasive source in the search for new molecular indicators of disease diagnosis, prognosis, and surveillance. In particular, proteomics represents an ideal strategy for the identification of urinary protein markers; thus, a urinomic approach could also represent a powerful tool in the investigation of the most common kidney cancer, which is clear cell Renal Cell Carcinoma (ccRCC). Currently, these tumors are classified after surgical removal using the TNM and nuclear grading systems and prognosis is usually predicted based upon staging. However, the aggressiveness and clinical outcomes of ccRCC remain heterogeneous within each stratified group, highlighting the need for novel molecular indicators that can predict the progression of these tumors. In our study, we explored the association between the urinary proteome and the ccRCC staging and grading classification. The urine proteome of 44 ccRCC patients with lesions of varying severity was analyzed via label-free proteomics. MS data revealed several proteins with altered abundance according to clinicopathological stratification. Specifically, we determined a panel of dysregulated proteins strictly related to stage and grade, suggesting the potential utility of MS-based urinomics as a complementary tool in the staging process of ccRCC.

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“…GDF15, a recently identified cachexia-inducing factor, was shown to be a promising target for treating cancer cachexia [ 30 ]. GDF15 induces cancer cachexia via its action on the hypothalamus to decrease appetite [ 31 ] and elicits a lipolytic response in adipose tissue [ 30 ]. High circulating levels of GDF15 are associated with weight loss and shorter survival in cancer patients [ 32 , 33 , 34 ].…”

Section: Cachexia-inducing Factorsmentioning

confidence: 99%

“…However, another study found no abnormal secretion of PTHrP from LLC cells compared with non-tumorigenic cell lines and a tumor cell line that does induce cachexia [ 47 ]. There was no significant difference in circulating PTHrP levels in mice bearing LLC tumors and control mice [ 31 ]. High levels of circulating PTHrP was shown to be associated with lower lean body mass and higher resting energy expenditure in patients with lung and colorectal cancer [ 46 , 48 ].…”

Section: Cachexia-inducing Factorsmentioning

confidence: 99%

Biomarkers for Cancer Cachexia: A Mini Review

Cao

Zhao

Jose

et al. 2021

IJMS

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Cancer cachexia is a common condition in many cancer patients, particularly those with advanced disease. Cancer cachexia patients are generally less tolerant to chemotherapies and radiotherapies, largely limiting their treatment options. While the search for treatments of this condition are ongoing, standards for the efficacy of treatments have yet to be developed. Current diagnostic criteria for cancer cachexia are primarily based on loss of body mass and muscle function. However, these criteria are rather limiting, and in time, when weight loss is noticeable, it may be too late for treatment. Consequently, biomarkers for cancer cachexia would be valuable adjuncts to current diagnostic criteria, and for assessing potential treatments. Using high throughput methods such as “omics approaches”, a plethora of potential biomarkers have been identified. This article reviews and summarizes current studies of biomarkers for cancer cachexia.

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GDF15/GFRAL Pathway as a Metabolic Signature for Cachexia in Patients with Cancer

Cited by 45 publications

References 89 publications

Pathophysiological pathways related to high plasma growth differentiation factor 15 concentrations in patients with heart failure

Pathophysiological pathways related to high plasma growth differentiation factor 15 concentrations in patients with heart failure

Does the Urinary Proteome Reflect ccRCC Stage and Grade Progression?

Biomarkers for Cancer Cachexia: A Mini Review

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