Clinical impact of soluble Neuropilin-1 in ovarian cancer patients and its association with its circulating ligands of the HGF/c-MET axis
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 (...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.974885/full |
| _version_ | 1811250087176699904 |
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| author | Daniel Martin Klotz Daniel Martin Klotz Daniel Martin Klotz Jan Dominik Kuhlmann Jan Dominik Kuhlmann Jan Dominik Kuhlmann Theresa Link Theresa Link Theresa Link Maren Goeckenjan Maren Goeckenjan Maren Goeckenjan Lorenz C. Hofbauer Lorenz C. Hofbauer Lorenz C. Hofbauer Andy Göbel Andy Göbel Andy Göbel Tilman D. Rachner Tilman D. Rachner Tilman D. Rachner Pauline Wimberger Pauline Wimberger Pauline Wimberger |
| author_facet | Daniel Martin Klotz Daniel Martin Klotz Daniel Martin Klotz Jan Dominik Kuhlmann Jan Dominik Kuhlmann Jan Dominik Kuhlmann Theresa Link Theresa Link Theresa Link Maren Goeckenjan Maren Goeckenjan Maren Goeckenjan Lorenz C. Hofbauer Lorenz C. Hofbauer Lorenz C. Hofbauer Andy Göbel Andy Göbel Andy Göbel Tilman D. Rachner Tilman D. Rachner Tilman D. Rachner Pauline Wimberger Pauline Wimberger Pauline Wimberger |
| author_sort | Daniel Martin Klotz |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T15:58:55Z |
| format | Article |
| id | doaj.art-03ee71a135cd4b958849b2d257f515b6 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-12T15:58:55Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-03ee71a135cd4b958849b2d257f515b62022-12-22T03:26:15ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-10-011210.3389/fonc.2022.974885974885Clinical impact of soluble Neuropilin-1 in ovarian cancer patients and its association with its circulating ligands of the HGF/c-MET axisDaniel Martin Klotz0Daniel Martin Klotz1Daniel Martin Klotz2Jan Dominik Kuhlmann3Jan Dominik Kuhlmann4Jan Dominik Kuhlmann5Theresa Link6Theresa Link7Theresa Link8Maren Goeckenjan9Maren Goeckenjan10Maren Goeckenjan11Lorenz C. Hofbauer12Lorenz C. Hofbauer13Lorenz C. Hofbauer14Andy Göbel15Andy Göbel16Andy Göbel17Tilman D. Rachner18Tilman D. Rachner19Tilman D. Rachner20Pauline Wimberger21Pauline Wimberger22Pauline Wimberger23Department of Gynecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, GermanyGerman Cancer Consortium (DKTK), partner site Dresden and German Cancer Research Center (DKFZ), Heidelberg, GermanyNational Center for Tumor Diseases (NCT), Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, GermanyDepartment of Gynecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, GermanyGerman Cancer Consortium (DKTK), partner site Dresden and German Cancer Research Center (DKFZ), Heidelberg, GermanyNational Center for Tumor Diseases (NCT), Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, GermanyDepartment of Gynecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, GermanyGerman Cancer Consortium (DKTK), partner site Dresden and German Cancer Research Center (DKFZ), Heidelberg, GermanyNational Center for Tumor Diseases (NCT), Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, GermanyDepartment of Gynecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, GermanyGerman Cancer Consortium (DKTK), partner site Dresden and German Cancer Research Center (DKFZ), Heidelberg, GermanyNational Center for Tumor Diseases (NCT), Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, GermanyGerman Cancer Consortium (DKTK), partner site Dresden and German Cancer Research Center (DKFZ), Heidelberg, GermanyNational Center for Tumor Diseases (NCT), Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, GermanyDivision of Endocrinology, Diabetes, and Bone Diseases, Department of Medicine III, Technische Universität Dresden, Dresden, GermanyGerman Cancer Consortium (DKTK), partner site Dresden and German Cancer Research Center (DKFZ), Heidelberg, GermanyNational Center for Tumor Diseases (NCT), Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, GermanyDivision of Endocrinology, Diabetes, and Bone Diseases, Department of Medicine III, Technische Universität Dresden, Dresden, GermanyGerman Cancer Consortium (DKTK), partner site Dresden and German Cancer Research Center (DKFZ), Heidelberg, GermanyNational Center for Tumor Diseases (NCT), Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, GermanyDivision of Endocrinology, Diabetes, and Bone Diseases, Department of Medicine III, Technische Universität Dresden, Dresden, GermanyDepartment of Gynecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, GermanyGerman Cancer Consortium (DKTK), partner site Dresden and German Cancer Research Center (DKFZ), Heidelberg, GermanyNational Center for Tumor Diseases (NCT), Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, GermanyBackgroundNeuropilin (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.https://www.frontiersin.org/articles/10.3389/fonc.2022.974885/fullovarian cancersoluble neuropilin-1prognosisblood-based biomarkerretrospective analysisHGF |
| spellingShingle | Daniel Martin Klotz Daniel Martin Klotz Daniel Martin Klotz Jan Dominik Kuhlmann Jan Dominik Kuhlmann Jan Dominik Kuhlmann Theresa Link Theresa Link Theresa Link Maren Goeckenjan Maren Goeckenjan Maren Goeckenjan Lorenz C. Hofbauer Lorenz C. Hofbauer Lorenz C. Hofbauer Andy Göbel Andy Göbel Andy Göbel Tilman D. Rachner Tilman D. Rachner Tilman D. Rachner Pauline Wimberger Pauline Wimberger Pauline Wimberger Clinical impact of soluble Neuropilin-1 in ovarian cancer patients and its association with its circulating ligands of the HGF/c-MET axis Frontiers in Oncology ovarian cancer soluble neuropilin-1 prognosis blood-based biomarker retrospective analysis HGF |
| title | Clinical impact of soluble Neuropilin-1 in ovarian cancer patients and its association with its circulating ligands of the HGF/c-MET axis |
| title_full | Clinical impact of soluble Neuropilin-1 in ovarian cancer patients and its association with its circulating ligands of the HGF/c-MET axis |
| title_fullStr | Clinical impact of soluble Neuropilin-1 in ovarian cancer patients and its association with its circulating ligands of the HGF/c-MET axis |
| title_full_unstemmed | Clinical impact of soluble Neuropilin-1 in ovarian cancer patients and its association with its circulating ligands of the HGF/c-MET axis |
| title_short | Clinical impact of soluble Neuropilin-1 in ovarian cancer patients and its association with its circulating ligands of the HGF/c-MET axis |
| title_sort | clinical impact of soluble neuropilin 1 in ovarian cancer patients and its association with its circulating ligands of the hgf c met axis |
| topic | ovarian cancer soluble neuropilin-1 prognosis blood-based biomarker retrospective analysis HGF |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.974885/full |
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