Chitra Subramanian1, Mark S Cohen2. 1. Department of Surgery, University of Michigan, Ann Arbor, Michigan. 2. Department of Surgery, University of Michigan, Ann Arbor, Michigan; Department of Pharmacology, University of Michigan, Ann Arbor, Michigan. Electronic address: cohenmar@med.umich.edu.
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.
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 carcinomapatients. 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 carcinomapatients.
Authors: Aung Naing; Razelle Kurzrock; Angelika Burger; Sachin Gupta; Xiudong Lei; Naifa Busaidy; David Hong; Helen X Chen; Lawrence A Doyle; Lance K Heilbrun; Eric Rohren; Chaan Ng; Chandtip Chandhasin; Patricia LoRusso Journal: Clin Cancer Res Date: 2011-07-12 Impact factor: 12.531
Authors: André P Fay; Aymen Elfiky; Gabriela H Teló; Rana R McKay; Marina Kaymakcalan; Paul L Nguyen; Anand Vaidya; Daniel T Ruan; Joaquim Bellmunt; Toni K Choueiri Journal: Crit Rev Oncol Hematol Date: 2014-06-04 Impact factor: 6.312
Authors: Matthias Kroiss; Marcus Quinkler; Sarah Johanssen; Nielka P van Erp; Nienke Lankheet; Alexander Pöllinger; Katharina Laubner; Christian J Strasburger; Stefanie Hahner; Hans-Helge Müller; Bruno Allolio; Martin Fassnacht Journal: J Clin Endocrinol Metab Date: 2012-07-26 Impact factor: 5.958
Authors: Karl Y Bilimoria; Wen T Shen; Dina Elaraj; David J Bentrem; David J Winchester; Electron Kebebew; Cord Sturgeon Journal: Cancer Date: 2008-12-01 Impact factor: 6.860
Authors: Ethan Cerami; Jianjiong Gao; Ugur Dogrusoz; Benjamin E Gross; Selcuk Onur Sumer; Bülent Arman Aksoy; Anders Jacobsen; Caitlin J Byrne; Michael L Heuer; Erik Larsson; Yevgeniy Antipin; Boris Reva; Arthur P Goldberg; Chris Sander; Nikolaus Schultz Journal: Cancer Discov Date: 2012-05 Impact factor: 39.397
Authors: Darshan S Chandrashekar; Bhuwan Bashel; Sai Akshaya Hodigere Balasubramanya; Chad J Creighton; Israel Ponce-Rodriguez; Balabhadrapatruni V S K Chakravarthi; Sooryanarayana Varambally Journal: Neoplasia Date: 2017-07-18 Impact factor: 5.715
Authors: Tatiana V Kudryashova; Swati Dabral; Soni S Pullamsetti; Elena A Goncharova; Sreenath Nayakanti; Arnab Ray; Dmitry A Goncharov; Theodore Avolio; Yuanjun Shen; Analise Rode; Andressa Pena; Lifeng Jiang; Derek Lin; Jeffrey Baust; Timothy N Bachman; Johannes Graumann; Clemens Ruppert; Andreas Guenther; Mario Schmoranzer; Yann Grobs; Sarah Eve Lemay; Eve Tremblay; Sandra Breuils-Bonnet; Olivier Boucherat; Ana L Mora; Horace DeLisser; Jing Zhao; Yutong Zhao; Sébastien Bonnet; Werner Seeger Journal: Circ Res Date: 2022-02-07 Impact factor: 17.367