Protein Expression of Cyclin B1, Transferrin Receptor, and Fibronectin Is Correlated with the Prognosis of Adrenal Cortical Carcinoma

BackgroundAdrenal cortical carcinoma (ACC) is a rare cancer with a variable prognosis. Several prognostic factors of ACC have been previously reported, but a proteomic analysis has not yet been performed. This study aimed to investigate prognostic biomarkers for ACC using a proteomic approach.Method...

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Main Authors: Sun Joon Moon, Jung Hee Kim, Sung Hye Kong, Chan Soo Shin
Format: Article
Language:English
Published: Korean Endocrine Society 2020-03-01
Series:Endocrinology and Metabolism
Subjects:
Online Access:https://e-enm.org/Synapse/Data/PDFData/2008ENM/enm-35-132.pdf
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author Sun Joon Moon
Jung Hee Kim
Sung Hye Kong
Chan Soo Shin
author_facet Sun Joon Moon
Jung Hee Kim
Sung Hye Kong
Chan Soo Shin
author_sort Sun Joon Moon
collection DOAJ
description BackgroundAdrenal cortical carcinoma (ACC) is a rare cancer with a variable prognosis. Several prognostic factors of ACC have been previously reported, but a proteomic analysis has not yet been performed. This study aimed to investigate prognostic biomarkers for ACC using a proteomic approach.MethodsWe used reverse-phase protein array data from The Cancer Proteome Atlas, and identified differentially expressed proteins in metastatic ACCs. Multivariate Cox regression analysis adjusted by age and staging was used for survival analysis, and the C-index and category-free net reclassification improvement (cfNRI) were utilized to evaluate additive prognostic value.ResultsIn 46 patients with ACC, cyclin B1, transferrin receptor (TfR1), and fibronectin were significantly overexpressed in patients with distant metastasis. In multivariate models, high expression of cyclin B1 and TfR1 was significantly associated with mortality (hazard ratio [HR], 6.13; 95% confidence interval [CI], 1.02 to 36.7; and HR, 6.59; 95% CI, 1.14 to 38.2; respectively), whereas high fibronectin expression was not (HR, 3.92; 95% CI, 0.75 to 20.4). Combinations of high cyclin B1/high TfR1, high cyclin B1/high fibronectin, and high TfR1/high fibronectin were strongly associated with mortality ([HR, 13.72; 95% CI, 1.89 to 99.66], [HR, 9.22; 95% CI, 1.34 to 63.55], and [HR, 18.59; 95% CI, 2.54 to 135.88], respectively). In reclassification analyses, cyclin B1, TfR1, fibronectin, and combinations thereof improved the prognostic performance (C-index, 0.78 to 0.82–0.86; cfNRI, all P values <0.05).ConclusionIn ACC patients, the overexpression of cyclin B1, TfR1, and fibronectin and combinations thereof were associated with poor prognosis.
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spelling doaj.art-eec52a1a8d3249778e50f886c8701fd72022-12-21T19:05:30ZengKorean Endocrine SocietyEndocrinology and Metabolism2093-596X2093-59782020-03-0135113214110.3803/EnM.2020.35.1.132Protein Expression of Cyclin B1, Transferrin Receptor, and Fibronectin Is Correlated with the Prognosis of Adrenal Cortical CarcinomaSun Joon Moon0Jung Hee Kim1Sung Hye Kong2Chan Soo Shin3Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, .KoreaDepartment of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, .KoreaDepartment of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, .KoreaDepartment of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, .KoreaBackgroundAdrenal cortical carcinoma (ACC) is a rare cancer with a variable prognosis. Several prognostic factors of ACC have been previously reported, but a proteomic analysis has not yet been performed. This study aimed to investigate prognostic biomarkers for ACC using a proteomic approach.MethodsWe used reverse-phase protein array data from The Cancer Proteome Atlas, and identified differentially expressed proteins in metastatic ACCs. Multivariate Cox regression analysis adjusted by age and staging was used for survival analysis, and the C-index and category-free net reclassification improvement (cfNRI) were utilized to evaluate additive prognostic value.ResultsIn 46 patients with ACC, cyclin B1, transferrin receptor (TfR1), and fibronectin were significantly overexpressed in patients with distant metastasis. In multivariate models, high expression of cyclin B1 and TfR1 was significantly associated with mortality (hazard ratio [HR], 6.13; 95% confidence interval [CI], 1.02 to 36.7; and HR, 6.59; 95% CI, 1.14 to 38.2; respectively), whereas high fibronectin expression was not (HR, 3.92; 95% CI, 0.75 to 20.4). Combinations of high cyclin B1/high TfR1, high cyclin B1/high fibronectin, and high TfR1/high fibronectin were strongly associated with mortality ([HR, 13.72; 95% CI, 1.89 to 99.66], [HR, 9.22; 95% CI, 1.34 to 63.55], and [HR, 18.59; 95% CI, 2.54 to 135.88], respectively). In reclassification analyses, cyclin B1, TfR1, fibronectin, and combinations thereof improved the prognostic performance (C-index, 0.78 to 0.82–0.86; cfNRI, all P values <0.05).ConclusionIn ACC patients, the overexpression of cyclin B1, TfR1, and fibronectin and combinations thereof were associated with poor prognosis.https://e-enm.org/Synapse/Data/PDFData/2008ENM/enm-35-132.pdfadrenocortical carcinomaprotein array analysisproteomicsprognosis
spellingShingle Sun Joon Moon
Jung Hee Kim
Sung Hye Kong
Chan Soo Shin
Protein Expression of Cyclin B1, Transferrin Receptor, and Fibronectin Is Correlated with the Prognosis of Adrenal Cortical Carcinoma
Endocrinology and Metabolism
adrenocortical carcinoma
protein array analysis
proteomics
prognosis
title Protein Expression of Cyclin B1, Transferrin Receptor, and Fibronectin Is Correlated with the Prognosis of Adrenal Cortical Carcinoma
title_full Protein Expression of Cyclin B1, Transferrin Receptor, and Fibronectin Is Correlated with the Prognosis of Adrenal Cortical Carcinoma
title_fullStr Protein Expression of Cyclin B1, Transferrin Receptor, and Fibronectin Is Correlated with the Prognosis of Adrenal Cortical Carcinoma
title_full_unstemmed Protein Expression of Cyclin B1, Transferrin Receptor, and Fibronectin Is Correlated with the Prognosis of Adrenal Cortical Carcinoma
title_short Protein Expression of Cyclin B1, Transferrin Receptor, and Fibronectin Is Correlated with the Prognosis of Adrenal Cortical Carcinoma
title_sort protein expression of cyclin b1 transferrin receptor and fibronectin is correlated with the prognosis of adrenal cortical carcinoma
topic adrenocortical carcinoma
protein array analysis
proteomics
prognosis
url https://e-enm.org/Synapse/Data/PDFData/2008ENM/enm-35-132.pdf
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