GDF-15: a novel serum marker for metastases in uveal melanoma patients

Suesskind, Daniela; Schatz, Andreas; Schnichels, Sven; Coupland, Sarah E.; Lake, Sarah L.; Wissinger, Bernd; Bartz‐Schmidt, Karl Ulrich; Henke-Fahle, Sigrid

doi:10.1007/s00417-011-1786-6

Cited by 38 publications

(29 citation statements)

References 31 publications

(35 reference statements)

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“…Elevated serum levels of MIA, S100-β, and osteopontin (OPN) correlated with liver UM metastases, and the combination of these three biomarkers enhanced the sensitivity and specificity in detecting hepatic metastases [324]. Serum levels of cytokeratin 18 (TPS) [325], insulin-like growth factor 1 (IGF1) [326], growth differentiation factor 15 (GDF15) [327], and Parkinson protein N7 (PARK7 or DJ-1) [328] are significantly more elevated in metastatic than in metastasis-free patients. An increase in VEGF on serial measurements might indicate the presence of metastases, but its value was limited by the large variability among patients [329].…”

Section: Biomarkersmentioning

confidence: 99%

The biology of uveal melanoma

Amaro

Gangemi

Piaggio

et al. 2017

Cancer Metastasis Rev

184

193

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Uveal melanoma (UM), a rare cancer of the eye, is distinct from cutaneous melanoma by its etiology, the mutation frequency and profile, and its clinical behavior including resistance to targeted therapy and immune checkpoint blockers. Primary disease is efficiently controlled by surgery or radiation therapy, but about half of UMs develop distant metastasis mostly to the liver. Survival of patients with metastasis is below 1 year and has not improved in decades. Recent years have brought a deep understanding of UM biology characterized by initiating mutations in the G proteins GNAQ and GNA11. Cytogenetic alterations, in particular monosomy of chromosome 3 and amplification of the long arm of chromosome 8, and mutation of the BRCA1-associated protein 1, BAP1, a tumor suppressor gene, or the splicing factor SF3B1 determine UM metastasis. Cytogenetic and molecular profiling allow for a very precise prognostication that is still not matched by efficacious adjuvant therapies. G protein signaling has been shown to activate the YAP/TAZ pathway independent of HIPPO, and conventional signaling via the mitogen-activated kinase pathway probably also contributes to UM development and progression. Several lines of evidence indicate that inflammation and macrophages play a pro-tumor role in UM and in its hepatic metastases. UM cells benefit from the immune privilege in the eye and may adopt several mechanisms involved in this privilege for tumor escape that act even after leaving the niche. Here, we review the current knowledge of the biology of UM and discuss recent approaches to UM treatment.

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Section: Biomarkersmentioning

confidence: 99%

The biology of uveal melanoma

Amaro

Gangemi

Piaggio

et al. 2017

Cancer Metastasis Rev

184

193

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“…15 was identified many years ago, the principal function, specific receptor, and signaling pathways of GDF-15 remained uncertain [13]. Increased GDF-15 expression is a common feature of many cancers [14][15][16][17] and serum GDF-15 levels are frequently elevated in metastatic tumors, often in parallel with the stages and extent of disease [18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Growth Differentiation Factor-15 (GDF-15) is a potential marker of radiation response and radiation sensitivity

Sándor

Schilling-Tóth

Kis

et al. 2015

Mutation Research/Genetic Toxicology and Environmental Mutagene

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“…In UM, a number of proteins have already been examined in patient sera including OPN [48], MIA [49], S100ß [50], GDF15 [51], PARK7 [52], ME20 [53], soluble c-Met [54] and IGF [55], each demonstrating varying degrees of sensitivity and specificity in the identification of patients with disseminated disease compared with metastasis-free UM patients and/or normal healthy controls. Of these proteins OPN, MIA, GDF15, PARK7 and ME20 were detected in the current study; however, only MIA and GDF15 demonstrated significantly higher levels in the secretome of UM compared with NCM, with no significant difference between the levels detected in HR- and LR-UM.…”

Section: Discussionmentioning

confidence: 99%

In-depth proteomic profiling of the uveal melanoma secretome

et al. 2016

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Uveal melanoma (UM), the most common primary intraocular tumour in adults, is characterised by a high frequency of metastases to the liver, typically with a fatal outcome. Proteins secreted from cancer cells (‘secretome’) are biologically important molecules thought to contribute to tumour progression. We examined the UM secretome by applying a label-free nanoLCMS/MS proteomic approach to profile proteins secreted into culture media by primary UM tumours with a high− (HR; n = 11) or low− (LR; n = 4) metastatic risk, compared to normal choroidal melanocytes (NCM) from unaffected post-mortem eyes. Across the three groups, 1843 proteins were identified at a 1% false discovery rate; 758 of these by at least 3 unique peptides, and quantified. The majority (539/758, 71%) of proteins were classified as secreted either by classical (144, 19%), non-classical (43, 6%) or exosomal (352, 46%) mechanisms. Bioinformatic analyzes showed that the secretome composition reflects biological differences and similarities of the samples. Ingenuity® pathway analysis of the secreted protein dataset identified abundant proteins involved in cell proliferation-, growth- and movement. Hepatic fibrosis/hepatic stellate cell activation and the mTORC1-S6K signalling axis were among the most differentially regulated biological processes in UM as compared with NCM. Further analysis of proteins upregulated ≥ 2 in HR-UM only, identified exosomal proteins involved in extracellular matrix remodelling and cancer cell migration/invasion; as well as classically secreted proteins, possibly representing novel biomarkers of metastatic disease. In conclusion, UM secretome analysis identifies novel proteins and pathways that may contribute to metastatic development at distant sites, particularly in the liver.

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GDF-15: a novel serum marker for metastases in uveal melanoma patients

Abstract: Our data suggest that GDF-15 can be used as a serum marker for the diagnosis of metastases in UM patients. Further data collection and analysis are necessary to evaluate a possible prognostic role of GDF-15 in predicting early metastases.

Cited by 38 publications

References 31 publications

The biology of uveal melanoma

The biology of uveal melanoma

Growth Differentiation Factor-15 (GDF-15) is a potential marker of radiation response and radiation sensitivity

In-depth proteomic profiling of the uveal melanoma secretome

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