title: Characterization and plasma measurement of the WE-14 peptide in patients with pheochromocytoma.
abstract: Granins and their derived peptides are valuable circulating biological markers of neuroendocrine tumors. The aim of the present study was to investigate the tumoral chromogranin A (CgA)-derived peptide WE-14 and the potential advantage to combine plasma WE-14 detection with the EM66 assay and the existing current CgA assay for the diagnosis of pheochromocytoma. Compared to healthy volunteers, plasma WE-14 levels were 5.4-fold higher in patients with pheochromocytoma, but returned to normal values after surgical resection of the tumor. Determination of plasma CgA and EM66 concentrations in the same group of patients revealed that the test assays for these markers had an overall 84% diagnostic sensitivity, which is identical to that determined for WE-14. However, we found that WE-14 measurement improved the diagnostic sensitivity when combined with the results of CgA or EM66 assays. By combining the results of the three assays, the sensitivity for the diagnosis of pheochromocytoma was increased to 95%. In fact, the combination of WE-14 with either CgA or EM66 test assays achieved 100% sensitivity for the diagnosis of paragangliomas and sporadic or malignant pheochromocytomas if taken separately to account for the heterogeneity of the tumor. These data indicate that WE-14 is produced in pheochromocytoma and secreted into the general circulation, and that elevated plasma WE-14 levels are correlated with the occurrence of this chromaffin cell tumor. In addition, in association with other biological markers, such as CgA and/or EM66, WE-14 measurement systematically improves the diagnostic sensitivity for pheochromocytoma. These findings support the notion that granin-processing products may represent complementary tools for the diagnosis of neuroendocrine tumors.
authors: Institut National de la Santé et de la Recherche Médicale (INSERM), U982, Mont-Saint-Aignan, France ; Normandy University, Normandy, France ; Rouen University, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine (IRIB), Mont-Saint-Aignan, France ; Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec, Canada.
authors: Johann
authors: J
authors: Guillemot
authors: Institut National de la Santé et de la Recherche Médicale (INSERM), U982, Mont-Saint-Aignan, France ; Normandy University, Normandy, France ; Rouen University, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine (IRIB), Mont-Saint-Aignan, France.
authors: Marlène
authors: M
authors: Guérin
authors: Institut National de la Santé et de la Recherche Médicale (INSERM), U982, Mont-Saint-Aignan, France ; Normandy University, Normandy, France ; Rouen University, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine (IRIB), Mont-Saint-Aignan, France.
authors: Erwan
authors: E
authors: Thouënnon
authors: Institut National de la Santé et de la Recherche Médicale (INSERM), U982, Mont-Saint-Aignan, France ; Normandy University, Normandy, France ; Rouen University, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine (IRIB), Mont-Saint-Aignan, France.
authors: Maité
authors: M
authors: Montéro-Hadjadje
authors: Institut National de la Santé et de la Recherche Médicale (INSERM), U982, Mont-Saint-Aignan, France ; Normandy University, Normandy, France ; Rouen University, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine (IRIB), Mont-Saint-Aignan, France.
authors: Jérôme
authors: J
authors: Leprince
authors: Institut National de la Santé et de la Recherche Médicale (INSERM), U982, Mont-Saint-Aignan, France ; Normandy University, Normandy, France ; Rouen University, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine (IRIB), Mont-Saint-Aignan, France ; Department of Endocrinology, Diabetes and Metabolic Diseases, Rouen University Hospital, Bois-Guillaume, France.
authors: Hervé
authors: H
authors: Lefebvre
authors: Department of Endocrinology, Hôpital de Brabois, University of Nancy, Nancy, France.
authors: Marc
authors: M
authors: Klein
authors: Unit of Endocrinology, Hôpital Notre-Dame de Bon Secours, Metz, France.
authors: Mihaela
authors: M
authors: Muresan
authors: Institut National de la Santé et de la Recherche Médicale (INSERM), U982, Mont-Saint-Aignan, France ; Normandy University, Normandy, France ; Rouen University, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine (IRIB), Mont-Saint-Aignan, France.
authors: Youssef
authors: Y
authors: Anouar
authors: Institut National de la Santé et de la Recherche Médicale (INSERM), U982, Mont-Saint-Aignan, France ; Normandy University, Normandy, France ; Rouen University, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine (IRIB), Mont-Saint-Aignan, France.
authors: Laurent
authors: L
authors: Yon
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000097:blood*; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D019439:Chromaffin Cells / Q000166:cytology; D053379:Chromogranin A / Q000097:blood*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000097:blood*; D018358:Neuroendocrine Tumors / Q000097:blood*; D010455:Peptides / Q000737:chemistry*; D010673:Pheochromocytoma / Q000097:blood*; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D015415:Biomarkers; D053379:Chromogranin A; D009363:Neoplasm Proteins; D010455:Peptides; C074381:chromogranin A-derived peptide, WE-14