Endocrinol Metab.  2020 Mar;35(1):132-141. 10.3803/EnM.2020.35.1.132.

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

Affiliations
  • 1Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea. jungheeendo@gmail.com
  • 2Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University College of Medicine, Seoul, Korea.

Abstract

BACKGROUND
Adrenal 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.
METHODS
We 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.
RESULTS
In 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).
CONCLUSION
In ACC patients, the overexpression of cyclin B1, TfR1, and fibronectin and combinations thereof were associated with poor prognosis.

Keyword

Adrenocortical carcinoma; Protein array analysis; Proteomics; Prognosis

MeSH Terms

Adrenocortical Carcinoma*
Biomarkers
Cyclin B1*
Cyclins*
Fibronectins*
Humans
Mortality
Neoplasm Metastasis
Prognosis*
Protein Array Analysis
Proteome
Proteomics
Receptors, Transferrin*
Transferrin*
Biomarkers
Cyclin B1
Cyclins
Fibronectins
Proteome
Receptors, Transferrin
Transferrin

Figure

  • Fig. 1 Volcano plot of differentially expressed proteins in adrenal cortical carcinoma patients according to metastasis. TfR1, transferrin receptor.

  • Fig. 2 Kaplan-Meier curves for overall survival based on the expression status of differentially expressed proteins. (A) Cyclin B1. (B) Transferrin receptor (TfR1). (C) Fibronectin. (D) Cyclin B1 and TfR1. (E) Cyclin B1 and fibronectin. (F) TfR1 and fibronectin. (G) Cyclin B1, TfR1, and fibronectin.


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