Evaluation of a 4-protein serum biomarker panel-biglycan, annexin-A6, myeloperoxidase, and protein S100-A9 (B-AMP)-for the detection of esophageal adenocarcinoma.

[esophageal adenocarcinoma]

Esophageal adenocarcinoma (EAC ) is associated with a dismal prognosis . The identification of cancer biomarkers can advance the possibility for early detection and better monitoring of tumor progression and /or response to therapy . The authors present results from the development of a serum-based , 4 -protein (biglycan , myeloperoxidase , annexin-A 6 , and protein S 100 -A 9 ) biomarker panel for EAC .A vertically integrated , proteomics-based biomarker discovery approach was used to identify candidate serum biomarkers for the detection of EAC . Liquid chromatography-tandem mass spectrometry analysis was performed on formalin-fixed , paraffin-embedded tissue samples that were collected from across the Barrett esophagus (BE )-EAC disease spectrum . The mass spectrometry-based spectral count data were used to guide the selection of candidate serum biomarkers . Then , the serum enzyme-linked immunosorbent assay data were validated in an independent cohort and were used to develop a multiparametric risk-assessment model to predict the presence of disease .With a minimum threshold of 10 spectral counts , 351 proteins were identified as differentially abundant along the spectrum of Barrett esophagus , high -grade dysplasia , and EAC (P <.05 ). Eleven proteins from this data set were then tested using enzyme-linked immunosorbent assays in serum samples , of which 5 proteins were significantly elevated in abundance among patients who had EAC compared with normal controls , which mirrored trends across the disease spectrum present in the tissue data . By using serum data , a Bayesian rule-learning predictive model with 4 biomarkers was developed to accurately classify disease class ; the cross-validation results for the merged data set yielded accuracy of 87 % and an area under the receiver operating characteristic curve of 93 %.Serum biomarkers hold significant promise for the early , noninvasive detection of EAC . Cancer 2014 . © 2014 American Cancer Society .

Diseases
Validation

Diseases presenting "cancer" symptom

achondroplasia

acute rheumatic fever

adrenal incidentaloma

alpha-thalassemia

benign recurrent intrahepatic cholestasis

cadasil

canavan disease

carcinoma of the gallbladder

cholangiocarcinoma

coats disease

congenital adrenal hyperplasia

congenital diaphragmatic hernia

cowden syndrome

cushing syndrome

cutaneous mastocytosis

dedifferentiated liposarcoma

dystrophic epidermolysis bullosa

epidermolysis bullosa simplex

erdheim-chester disease

erythropoietic protoporphyria

esophageal adenocarcinoma

esophageal carcinoma

esophageal squamous cell carcinoma

familial hypocalciuric hypercalcemia

familial mediterranean fever

gm1 gangliosidosis

heparin-induced thrombocytopenia

hereditary cerebral hemorrhage with amyloidosis

hirschsprung disease

hodgkin lymphoma, classical

inclusion body myositis

junctional epidermolysis bullosa

kabuki syndrome

kallmann syndrome

kindler syndrome

lamellar ichthyosis

liposarcoma

locked-in syndrome

lymphangioleiomyomatosis

monosomy 21

neuralgic amyotrophy

oculocutaneous albinism

oligodontia

oral submucous fibrosis

papillon-lefèvre syndrome

pendred syndrome

pleomorphic liposarcoma

primary effusion lymphoma

proteus syndrome

pyomyositis

pyruvate dehydrogenase deficiency

severe combined immunodeficiency

sneddon syndrome

systemic capillary leak syndrome

triple a syndrome

von hippel-lindau disease

waldenström macroglobulinemia

well-differentiated liposarcoma

werner syndrome

wiskott-aldrich syndrome

wolf-hirschhorn syndrome

x-linked adrenoleukodystrophy

This symptom has already been validated