Prognostic relevance of longitudinal HGF levels in serum of patients with ovarian cancer

The pleiotropic protein hepatocyte growth factor (HGF) is the only known ligand of the tyrosine kinase mesenchymal–epithelial transition (cMET) receptor. The HGF/cMET pathway mediates invasion and migration of ovarian cancer cells, and upregulation of HGF/cMET pathway components has been associated...

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Autores principales:	Daniel Martin Klotz, Theresa Link, Pauline Wimberger, Jan Dominik Kuhlmann
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	biomarker cMET HGF ovarian cancer prognosis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/cf6cb568631c407b9309e6601d063dd2
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spelling	oai:doaj.org-article:cf6cb568631c407b9309e6601d063dd22021-12-02T10:31:06ZPrognostic relevance of longitudinal HGF levels in serum of patients with ovarian cancer1878-02611574-789110.1002/1878-0261.12949https://doaj.org/article/cf6cb568631c407b9309e6601d063dd22021-12-01T00:00:00Zhttps://doi.org/10.1002/1878-0261.12949https://doaj.org/toc/1574-7891https://doaj.org/toc/1878-0261The pleiotropic protein hepatocyte growth factor (HGF) is the only known ligand of the tyrosine kinase mesenchymal–epithelial transition (cMET) receptor. The HGF/cMET pathway mediates invasion and migration of ovarian cancer cells, and upregulation of HGF/cMET pathway components has been associated with poor prognosis. This study investigated the clinical relevance of circulating HGF in serum of patients with ovarian cancer. Serum HGF (sHGF) was determined by enzyme‐linked immunosorbent assay in a total of 471 serum samples from 82 healthy controls and 113 patients with ovarian cancer (88.5% with ≥ FIGO III). Patient samples were collected at primary diagnosis and at four follow‐up time points throughout treatment and at disease recurrence. Patients with ovarian cancer showed elevated median sHGF levels at primary diagnosis, and sHGF levels transiently increased after surgery and normalized in the course of chemotherapy, even dropping below initial baseline. Higher levels of sHGF were an independent predictor for shorter overall survival (OS) (a) at primary diagnosis (HR = 0.41, 95% CI: 0.22–0.78, P = 0.006), (b) at longitudinal follow‐up time points (after surgery and before/during/after chemotherapy), (c) along the patients’ individual dynamics (HR = 0.21, 95% CI: 0.07–0.63, P = 0.005), and (d) among a subgroup analysis of patients with BRCA1/2 wild‐type ovarian cancer. This is the first study proposing sHGF as an independent prognostic biomarker for ovarian cancer at primary diagnosis and in the course of platinum‐based chemotherapy, irrespective of the postoperative residual disease after surgical debulking. sHGF could be implemented into clinical diagnostics as a CA125 auxiliary tumor marker for individualized prognosis stratification and sHGF‐guided therapy monitoring.Daniel Martin KlotzTheresa LinkPauline WimbergerJan Dominik KuhlmannWileyarticlebiomarkercMETHGFovarian cancerprognosisNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENMolecular Oncology, Vol 15, Iss 12, Pp 3626-3638 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	biomarker cMET HGF ovarian cancer prognosis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	biomarker cMET HGF ovarian cancer prognosis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Daniel Martin Klotz Theresa Link Pauline Wimberger Jan Dominik Kuhlmann Prognostic relevance of longitudinal HGF levels in serum of patients with ovarian cancer
description	The pleiotropic protein hepatocyte growth factor (HGF) is the only known ligand of the tyrosine kinase mesenchymal–epithelial transition (cMET) receptor. The HGF/cMET pathway mediates invasion and migration of ovarian cancer cells, and upregulation of HGF/cMET pathway components has been associated with poor prognosis. This study investigated the clinical relevance of circulating HGF in serum of patients with ovarian cancer. Serum HGF (sHGF) was determined by enzyme‐linked immunosorbent assay in a total of 471 serum samples from 82 healthy controls and 113 patients with ovarian cancer (88.5% with ≥ FIGO III). Patient samples were collected at primary diagnosis and at four follow‐up time points throughout treatment and at disease recurrence. Patients with ovarian cancer showed elevated median sHGF levels at primary diagnosis, and sHGF levels transiently increased after surgery and normalized in the course of chemotherapy, even dropping below initial baseline. Higher levels of sHGF were an independent predictor for shorter overall survival (OS) (a) at primary diagnosis (HR = 0.41, 95% CI: 0.22–0.78, P = 0.006), (b) at longitudinal follow‐up time points (after surgery and before/during/after chemotherapy), (c) along the patients’ individual dynamics (HR = 0.21, 95% CI: 0.07–0.63, P = 0.005), and (d) among a subgroup analysis of patients with BRCA1/2 wild‐type ovarian cancer. This is the first study proposing sHGF as an independent prognostic biomarker for ovarian cancer at primary diagnosis and in the course of platinum‐based chemotherapy, irrespective of the postoperative residual disease after surgical debulking. sHGF could be implemented into clinical diagnostics as a CA125 auxiliary tumor marker for individualized prognosis stratification and sHGF‐guided therapy monitoring.
format	article
author	Daniel Martin Klotz Theresa Link Pauline Wimberger Jan Dominik Kuhlmann
author_facet	Daniel Martin Klotz Theresa Link Pauline Wimberger Jan Dominik Kuhlmann
author_sort	Daniel Martin Klotz
title	Prognostic relevance of longitudinal HGF levels in serum of patients with ovarian cancer
title_short	Prognostic relevance of longitudinal HGF levels in serum of patients with ovarian cancer
title_full	Prognostic relevance of longitudinal HGF levels in serum of patients with ovarian cancer
title_fullStr	Prognostic relevance of longitudinal HGF levels in serum of patients with ovarian cancer
title_full_unstemmed	Prognostic relevance of longitudinal HGF levels in serum of patients with ovarian cancer
title_sort	prognostic relevance of longitudinal hgf levels in serum of patients with ovarian cancer
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/cf6cb568631c407b9309e6601d063dd2
work_keys_str_mv	AT danielmartinklotz prognosticrelevanceoflongitudinalhgflevelsinserumofpatientswithovariancancer AT theresalink prognosticrelevanceoflongitudinalhgflevelsinserumofpatientswithovariancancer AT paulinewimberger prognosticrelevanceoflongitudinalhgflevelsinserumofpatientswithovariancancer AT jandominikkuhlmann prognosticrelevanceoflongitudinalhgflevelsinserumofpatientswithovariancancer
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Prognostic relevance of longitudinal HGF levels in serum of patients with ovarian cancer

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