Molecular classification and prognostication of adrenocortical tumors by transcriptome profiling
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Abstract
PURPOSE: Our understanding of adrenocortical carcinoma (ACC) has improved considerably, yet many unanswered questions remain. For instance, can molecular subtypes of ACC be identified? If so, what is their underlying pathogenetic basis and do they possess clinical significance? EXPERIMENTAL DESIGN: We did a whole genome gene expression study of a large cohort of adrenocortical tissues annotated with clinicopathologic data. Using Affymetrix Human Genome U133 Plus 2.0 oligonucleotide arrays, transcriptional profiles were generated for 10 normal adrenal cortices (NC), 22 adrenocortical adenomas (ACA), and 33 ACCs. RESULTS: The overall classification of adrenocortical tumors was recapitulated using principal component analysis of the entire data set. The NC and ACA cohorts showed little intragroup variation, whereas the ACC cohort revealed much greater variation in gene expression. A robust list of 2,875 differentially expressed genes in ACC compared with both NC and ACA was generated and used in functional enrichment analysis to find pathways and attributes of biological significance. Cluster analysis of the ACCs revealed two subtypes that reflected tumor proliferation, as measured by mitotic counts and cell cycle genes. Kaplan-Meier analysis of these ACC clusters showed a significant difference in survival (P < 0.020). Multivariate Cox modeling using stage, mitotic rate, and gene expression data as measured by the first principal component for ACC samples showed that gene expression data contains significant independent prognostic information (P < 0.017). CONCLUSIONS: This study lays the foundation for the molecular classification and prognostication of adrenocortical tumors and also provides a rich source of potential diagnostic and prognostic markers.
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Giordano et al identified unique transcriptionally activated (12q and 5q) and repressed (11q, 1p, and 17p) chromosomal regions in 33 ACCs vs 22 ACAs in a microarray study.
“Giordano et al (192) identified unique transcriptionally activated (12q and 5q) and repressed (11q, 1p, and 17p) chromosomal regions in 33 ACCs vs 22 ACAs in a microarray study”
From Adrenocortical carcinoma (2014) · cites this paper as [192]
ACAs and ACCs have distinct expression profiles.
“ACAs and ACCs have distinct expression profiles (174, 190–192).”
From Adrenocortical carcinoma (2014) · cites this paper as [192]
ACCs with high histological grade exhibit marked overexpression of cell cycle and functional aneuploidy genes, which correlates with decreased overall survival.
“Giordano et al (192) determined that ACCs with high histological grade exhibited marked overexpression of cell cycle and functional aneuploidy genes, which correlated with decreased overall survival.”
From Adrenocortical carcinoma (2014) · cites this paper as [192]
Increased expression of VEGF correlates with expression of IGF2.
“The increased expression of VEGF correlates with the expression of IGF2 (192).”
From Adrenocortical carcinoma (2014) · cites this paper as [192]
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Papiez, A., Marczyk, M., Polanska, J., & Polanski, A. (2019) · Bioinformatics · doi:10.1093/bioinformatics/bty900 · Cited by 26 · see citing works
- Authors
- Giordano, T. J., Kuick, R., Else, T., Gauger, P. G., Vinco, M., Bauersfeld, J., Sanders, D., Thomas, D. G., Doherty, G., & Hammer, G.
- Affiliations
- 1Pathology, Departments of
- 2Biostatistics Core,
- 3Internal Medicine, and
- University of Michigan (US)
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2009-01-15
- Volume
- 15
- Issue
- 2
- Pages
- 668-676
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- PMC
- PMC2629378
- OpenAlex
- W2138551378
- Cited by
- 401
- References
- 52
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 11 · 2023: 19 · 2022: 19 · 2021: 26 · 2020: 27 · 2019: 29 · 2018: 29 · 2017: 18 · 2016: 22 · 2015: 33 · 2014: 23 · 2013: 25 · 2012: 23
- FWCI
- 34.47
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Michigan
- University of Michigan Comprehensive Cancer Center
- National Cancer Institute (5P30 CA 46592, P30CA046592)
- Topics
- Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Health Sciences › Medicine › Neurology › Neuroblastoma Research and Treatments
- Keywords
- adrenocortical carcinoma, adrenal adenoma, adrenocortical tumors, molecular classification, gene expression profiling, gene expression, molecular subtypes, prognostic factors, tumor cell proliferation, mitotic activity, cell cycle genes, survival
- MeSH terms
- Adrenal Cortex, Adrenal Cortex Neoplasms, Humans, Immunohistochemistry, Prognosis, Transcription, Genetic, Cohort Studies, Cluster Analysis, Proportional Hazards Models, Genome, Cyclin E, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Cell Line, Tumor
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