Over expression of DNA damage and cell cycle dependent proteins are associated with poor survival in patients with adrenocortical carcinoma.

Abstract

BACKGROUND:

Adrenocortical carcinoma is a rare and aggressive malignancy with poor survival. With limited treatment options and high risk of relapse, identifying improved targets and therapies for adrenocortical carcinoma is important. We hypothesized that analysis of the database of The Cancer Genome Atlas could identify important novel biomarkers for improved therapeutic targeting of adrenocortical carcinoma.

METHODS:

We utilized the University of Alabama interactive web resource to identify novel biomarkers observed in 79 adrenocortical carcinoma patients. Identified biomarkers were then examined for prognostic correlations using the cBioPortal and analyzed for statistical significance using STATA 13.0.

RESULTS:

The Cancer Genome Atlas data mining in the University of Alabama interactive web resource for pathways associated with poor survival of patients with adrenocortical carcinoma revealed significant upregulation of genes involved in DNA damage and regulation of cell-cycle pathways, such as AURKA, AURKB, CDK1, CDK4, CDK6, PLK1, CHEK1, CHEK2, CDC7, BUB3, and MCM3 (P < .001-.05). On outcome correlation, greater expression levels of all the genes except CDK4 were associated with worse survival compared with medium or low levels of gene expression (P < .001 all) irrespective of age orsex. Consistent with our University of Alabama interactive web resource findings, data mining in the cBioPortal also revealed upregulation of genes regulating DNA-damage and cell cycle-related genes in 82% of patients (z score = 1.5).

CONCLUSION:

Large data mining from the The Cancer Genome Atlas and cBioPortal databases identified overexpression of genes involved in DNA damage and those regulating pathways of the cell cycle, which correlated with poorer overall survival in adrenocortical carcinoma patients.

• Authors: Chitra Subramanian, Mark S Cohen
• Journal: Surgery (Surgery) Vol. 165 Issue 1 Pg. 202-210 (01 2019) ISSN: 1532-7361 [Electronic] United States
• PMID: 30413320 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers, Tumor
• Cell Cycle Proteins
• IRF3 protein, human
• Interferon Regulatory Factor-3
• Microfilament Proteins
• Neuropeptides
• Nuclear Proteins
• Pyruvate Dehydrogenase Acetyl-Transferring Kinase
• RNA, Messenger
• ectodermal-neural cortex 1 protein
• FN3KRP protein, human
• Phosphotransferases (Alcohol Group Acceptor)
• Protein Serine-Threonine Kinases
• PRKCA protein, human
• Protein Kinase C-alpha
• CAMKK1 protein, human
• Calcium-Calmodulin-Dependent Protein Kinase Kinase
• DUSP5 protein, human
• Dual-Specificity Phosphatases

Topics

• Adrenal Cortex Neoplasms (genetics, metabolism, mortality)
• Adrenocortical Carcinoma (genetics, metabolism, mortality)
• Biomarkers, Tumor (genetics, metabolism)
• Calcium-Calmodulin-Dependent Protein Kinase Kinase (genetics, metabolism)
• Cell Cycle Proteins (genetics, metabolism)
• DNA Damage
• Datasets as Topic
• Down-Regulation
• Dual-Specificity Phosphatases (genetics, metabolism)
• Female
• Humans
• Interferon Regulatory Factor-3 (genetics, metabolism)
• Male
• Microfilament Proteins (genetics, metabolism)
• Neuropeptides (genetics, metabolism)
• Nuclear Proteins (genetics, metabolism)
• Phosphotransferases (Alcohol Group Acceptor) (genetics, metabolism)
• Prognosis
• Protein Kinase C-alpha (genetics, metabolism)
• Protein Serine-Threonine Kinases (genetics, metabolism)
• Pyruvate Dehydrogenase Acetyl-Transferring Kinase
• RNA, Messenger (metabolism)
• Up-Regulation