The levels of soluble cMET ectodomain in the blood of patients with ovarian cancer are an independent prognostic biomarker

Klotz, Daniel Martin; Link, Theresa; Goeckenjan, Maren; Wimberger, Pauline; Kuhlmann, Jan Dominik

doi:10.1002/1878-0261.12939

Cited by 5 publications

(9 citation statements)

References 51 publications

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“…The statistical analysis was conducted with R, Version 3.6.2 and GraphPad Prism version 8.4.3 (GraphPad Software, La Jolla, CA, USA) as described previously (26)(27)(28), and listed in each figure legend. P-values < 0.05 were considered statistically significant.…”

Section: Discussionmentioning

confidence: 99%

“…Serum preparation from blood-samples obtained at primary diagnosis of ovarian cancer was performed, as described previously (26)(27)(28). Briefly, sample processing occurred within 1 h of blood drawing.…”

Section: Serum Preparation and Detection Of Snrp-1mentioning

confidence: 99%

“…We hypothesized that there could be an association between the level of sNRP-1 and associated ligands in the blood of ovarian cancer patients. We took advantage of our previous studies on ovarian cancer, which demonstrated the prognostic relevance of both sHGF levels and the soluble ectodomain of its receptor c-MET (sMET) (26,27). Corresponding data on sHGF and sMET levels were available in 35/88 and 26/88 of our patients from two previous studies of our group, respectively (26,27).…”

Section: Association Of Snrp-1 With Serum Levels Of Hgf and The Solub...mentioning

confidence: 99%

“…We took advantage of our previous studies on ovarian cancer, which demonstrated the prognostic relevance of both sHGF levels and the soluble ectodomain of its receptor c-MET (sMET) (26,27). Corresponding data on sHGF and sMET levels were available in 35/88 and 26/88 of our patients from two previous studies of our group, respectively (26,27). This number of matching samples allowed us to investigate whether there was a proportional serological concentration gradient of sNRP-1 and its functionally related proteins sHGF and sMET.…”

Section: Association Of Snrp-1 With Serum Levels Of Hgf and The Solub...mentioning

confidence: 99%

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Clinical impact of soluble Neuropilin-1 in ovarian cancer patients and its association with its circulating ligands of the HGF/c-MET axis

Klotz

Kuhlmann²,

Link³

et al. 2022

Front. Oncol.

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BackgroundNeuropilin (NRP) is a transmembrane protein, which has been shown to be a pro-angiogenic mediator and implicated as a potential driver of cancer progression. NRP-1 up-regulation in ovarian cancer tissue predicts poor prognosis. However, the clinical relevance of the soluble form of NRP-1 (sNRP-1) as a circulating biomarker in ovarian cancer patients is unknown.Methods/patients cohortsNRP-1 levels were quantified in a cohort of 88 clinically documented ovarian cancer patients by a commercially available sNRP-1 enzyme-linked immunosorbent assay (ELISA) kit (Biomedica, Vienna, Austria). Patients (81.8% with FIGOIII/IV) received primary cytoreductive surgery with the aim of macroscopic complete resection (achieved in 55.7% of patients) and the recommendation of adjuvant chemotherapy in line with national guidelines.ResultsHigher levels of sNRP-1 reflected more advanced disease (FIGO III/IV) and indicated a trend towards suboptimal surgical outcome, i.e. any residual tumor. sNRP-1 was neither related to the patients’ age nor the BRCA1/2 mutational status. Patients with higher sNRP-1 levels at primary diagnosis had a significantly reduced progression-free survival (PFS) (HR = 0.541, 95%CI: 0.304 - 0.963; p = 0.037) and overall survival (OS) (HR = 0.459, 95%CI: 0.225 - 0.936; p = 0.032). Principal component analysis showed that sNRP-1 levels were unrelated to the circulating hepatocyte growth factor (HGF) and the soluble ectodomain of its receptor the tyrosine kinase mesenchymal–epithelial transition (c-MET), suggesting that there is no proportional serological concentration gradient of soluble components of the NRP-1/HGF/c-MET signaling axis.ConclusionsIn line with the previously shown tissue-based prognostic role, we demonstrated for the first time that sNRP-1 can also act as a readily accessible, prognostic biomarker in the circulation of patients with ovarian cancer at primary diagnosis. Given its known role in angiogenesis and conferring resistance to the poly ADP-ribose polymerase (PARP) inhibitor olaparib in vitro, our results encourage more detailed investigation into sNRP-1 as a potential predictive biomarker for bevacizumab and/or PARP-inhibitor treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Serum Preparation and Detection Of Snrp-1mentioning

confidence: 99%

Section: Association Of Snrp-1 With Serum Levels Of Hgf and The Solub...mentioning

confidence: 99%

Section: Association Of Snrp-1 With Serum Levels Of Hgf and The Solub...mentioning

confidence: 99%

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Clinical impact of soluble Neuropilin-1 in ovarian cancer patients and its association with its circulating ligands of the HGF/c-MET axis

Klotz

Kuhlmann²,

Link³

et al. 2022

Front. Oncol.

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“…Soluble forms of epidermal growth factor receptor family members (EGFR and ERBB2) and other receptor tyrosine kinases (e.g. c-Met and Axl) are abnormal in the serum of cancer patients [101][102][103].…”

Section: Soluble Receptor As Biomarkersmentioning

confidence: 99%

Soluble forms of cytokine and growth factor receptors: mechanisms of generation and modes of action in the regulation of local and systemic inflammation

Kefaloyianni

2022

FEBS Letters

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Cytokine and growth factor receptors are usually transmembrane proteins, but they can also exist in soluble forms, either through cleavage and release of their ligand-binding extracellular domain or through the secretion of a soluble isoform. As an extension of this concept, transmembrane receptors on exosomes released into the circulation may act similarly to circulating soluble receptors. These soluble receptors add to the complexity of cytokine and growth factor signalling: they can function as decoy receptor that compete for ligand binding with their respective membrane-bound forms thereby attenuating signalling, or stabilize their ligands, or activate additional signalling events through interactions with other cell-surface proteins. Their soluble nature allows for a functional role away from the production sites, in remote cell types and organs. Accumulating evidence demonstrates that soluble receptors participate in the regulation and orchestration of various key cellular processes, particularly inflammatory responses. In this review, we will discuss release mechanisms of soluble cytokine and growth factor receptors, their mechanisms of action and strategies for targeting their pathways in disease.

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MicroRNAs and proteolytic cleavage of receptors in cancers: A comprehensive review of regulatory interactions and therapeutic implications

Hosseinpour-Soleimani,

Salmasi,

Ghasemi

et al. 2024

Heliyon

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The levels of soluble cMET ectodomain in the blood of patients with ovarian cancer are an independent prognostic biomarker

Cited by 5 publications

References 51 publications

Clinical impact of soluble Neuropilin-1 in ovarian cancer patients and its association with its circulating ligands of the HGF/c-MET axis

Clinical impact of soluble Neuropilin-1 in ovarian cancer patients and its association with its circulating ligands of the HGF/c-MET axis

Soluble forms of cytokine and growth factor receptors: mechanisms of generation and modes of action in the regulation of local and systemic inflammation

MicroRNAs and proteolytic cleavage of receptors in cancers: A comprehensive review of regulatory interactions and therapeutic implications

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