title: Low molecular weight proteomic information distinguishes metastatic from benign pheochromocytoma.
abstract: Metastatic lesions occur in up to 36% of patients with pheochromocytoma. Currently there is no way to reliably detect or predict which patients are at risk for metastatic pheochromocytoma. Thus, the discovery of biomarkers that could distinguish patients with benign disease from those with metastatic disease would be of great clinical value. Using surface-enhanced laser desorption ionization protein chips combined with high-resolution mass spectrometry, we tested the hypothesis that pheochromocytoma pathologic states can be reflected as biomarker information within the low molecular weight (LMW) region of the serum proteome. LMW protein profiles were generated from the serum of 67 pheochromocytoma patients from four institutions and analyzed by two different bioinformatics approaches employing pattern recognition algorithms to determine if the LMW component of the circulatory proteome contains potentially useful discriminatory information. Both approaches were able to identify combinations of LMW molecules which could distinguish all metastatic from all benign pheochromocytomas in a separate blinded validation set. In conclusion, for this study set low molecular mass biomarker information correlated with pheochromocytoma pathologic state using blinded validation. If confirmed in larger validation studies, efforts to identify the underlying diagnostic molecules by sequencing would be warranted. In the future, measurement of these biomarkers could be potentially used to improve the ability to identify patients with metastatic disease.
authors.affiliation: Reproductive Biology and Medicine Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892-1109, USA.
authors.forename: F M
authors.initials: FM
authors.lastname: Brouwers
authors.forename: E F
authors.initials: EF
authors.lastname: Petricoin
authors.forename: L
authors.initials: L
authors.lastname: Ksinantova
authors.forename: J
authors.initials: J
authors.lastname: Breza
authors.forename: V
authors.initials: V
authors.lastname: Rajapakse
authors.forename: S
authors.initials: S
authors.lastname: Ross
authors.forename: D
authors.initials: D
authors.lastname: Johann
authors.forename: M
authors.initials: M
authors.lastname: Mannelli
authors.forename: B L
authors.initials: BL
authors.lastname: Shulkin
authors.forename: R
authors.initials: R
authors.lastname: Kvetnansky
authors.forename: G
authors.initials: G
authors.lastname: Eisenhofer
authors.forename: M M
authors.initials: MM
authors.lastname: Walther
authors.forename: B A
authors.initials: BA
authors.lastname: Hitt
authors.forename: T P
authors.initials: TP
authors.lastname: Conrads
authors.forename: T D
authors.initials: TD
authors.lastname: Veenstra
authors.forename: D P
authors.initials: DP
authors.lastname: Mannion
authors.forename: M R
authors.initials: MR
authors.lastname: Wall
authors.forename: G M
authors.initials: GM
authors.lastname: Wolfe
authors.forename: V A
authors.initials: VA
authors.lastname: Fusaro
authors.forename: L A
authors.initials: LA
authors.lastname: Liotta
authors.forename: K
authors.initials: K
authors.lastname: Pacak
mesh_terms: D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000175:diagnosis* / Q000473:pathology; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D002648:Child; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000097:blood*; D010673:Pheochromocytoma / Q000175:diagnosis* / Q000473:pathology; D020543:Proteome / Q000032:analysis*; D040901:Proteomics
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D020543:Proteome