Gene expression profiling reveals a new classification of adrenocortical tumors and identifies molecular predictors of malignancy and survival
Open accessAbstract
PURPOSE: Adrenocortical tumors, especially cancers, remain challenging both for their diagnosis and prognosis assessment. The aim of this article is to identify molecular predictors of malignancy and of survival. PATIENTS AND METHODS: One hundred fifty-three unilateral adrenocortical tumors were studied by microarray (n = 92) or reverse transcription quantitative polymerase chain reaction (n = 148). A two-gene predictor of malignancy was built using the disease-free survival as the end point in a training cohort (n = 47), then validated in an independent validation cohort (n = 104). The best candidate genes were selected using Cox models, and the best gene combination was validated using the log-rank test. Similarly, for malignant tumors, a two-gene predictor of survival was built using the overall survival as the end point in a training cohort (n = 23), then tested in an independent validation cohort (n = 35). RESULTS: Unsupervised clustering analysis discriminated robustly the malignant and benign tumors, and identified two groups of malignant tumors with very different outcome. The combined expression of DLG7 and PINK1 was the best predictor of disease-free survival (log-rank P approximately 10(-12)), could overcome the uncertainties of intermediate pathological Weiss scores, and remained significant after adjustment to the Weiss score (P < 1.3 x 10(-2)). Among the malignant tumors, the combined expression of BUB1B and PINK1 was the best predictor of overall survival (P < 2 x 10(-6)), and remained significant after adjusting for MacFarlane staging (P < .005). CONCLUSION: Gene expression analysis unravels two distinct groups of adrenocortical carcinomas. The molecular predictors of malignancy and of survival are reliable and provide valuable independent information in addition to pathology and tumor staging. These original tools should provide important improvements for adrenal tumors management.
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ACCs with poor outcome are enriched for genes involved in cell cycle and proliferation, whereas ACCs in the better outcome group exhibit overexpression of genes involved in differentiation, metabolism, and intracellular transport.
“ACCs with poor outcome were enriched for genes involved in cell cycle and proliferation, whereas ACCs in the better outcome group exhibited overexpression of genes involved in differentiation, metabolism, and intracellular transport.”
From Adrenocortical carcinoma (2014) · cites this paper as [191]
Expression levels of DLG7 and PINK1 identify subgroups of ACCs with distinct disease-free survival, regardless of tumor grade.
“Similarly, the expression levels of DLG7 and PINK1 identified subgroups of ACCs with distinct disease-free survival, regardless of tumor grade (191).”
From Adrenocortical carcinoma (2014) · cites this paper as [191]
Expression levels of BUB1B and PINK1 alone identify subgroups of ACCs with different overall survival, regardless of tumor stage.
“Expression levels of BUB1B and PINK1 alone identified subgroups of ACCs with different overall survival, regardless of tumor stage.”
From Adrenocortical carcinoma (2014) · cites this paper as [191]
Cluster analysis of ACCs reveals 2 distinct groups with different genetic signatures and concomitant distinct clinical outcomes.
“In another study, cluster analysis of ACCs again revealed 2 distinct groups with different genetic signatures and concomitant distinct clinical outcomes.”
From Adrenocortical carcinoma (2014) · cites this paper as [191]
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 [191]
High IGF2 expression levels in adrenal tumors are associated with a 5-fold increased risk for recurrence and a shorter disease-free survival.
“High IGF2 expression levels in adrenal tumors, when analyzing malignant and benign tumors, are associated with a 5-fold increased risk for recurrence and a shorter disease-free survival (184, 191).”
From Adrenocortical carcinoma (2014) · cites this paper as [191]
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- Authors
- de Reyniès, A., Assié, G., Rickman, D. S., Tissier, F., Groussin, L., René-Corail, F., Dousset, B., Bertagna, X., Clauser, E., & Bertherat, J.
- Affiliations
- From the Programme Cartes d'Identité des Tumeurs, Ligue Nationale Contre Le Cancer; Institut National de la Santé et de la Recherche Médicale, Unité 567, Centre National de La Recherche Scientifique, Unité Mixte de Recherche 8104, Institut Cochin, Endocrinology, Metabolism & Cancer Department; Université Paris Descartes; Department of Endocrinology, Department of Pathology, Unit of Digestive and Endocrine Surgery, Center for Rare Adrenal Diseases, Oncogenetic Unit, Assistance Publique Hôpitaux de Paris,...
- Centre National de la Recherche Scientifique (FR)
- Venue
- Journal of Clinical Oncology
- Published
- 2009-03-01
- Volume
- 27
- Issue
- 7
- Pages
- 1108-1115
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2145168501
- Cited by
- 382
- References
- 45
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 6 · 2023: 15 · 2022: 29 · 2021: 23 · 2020: 21 · 2019: 16 · 2018: 26 · 2017: 25 · 2016: 30 · 2015: 26 · 2014: 24 · 2013: 29 · 2012: 24
- FWCI
- 32.48
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- 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 › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
- Keywords
- adrenocortical tumors, adrenocortical carcinoma, gene expression profiling, molecular classification, malignancy prediction, survival prediction, PINK1, BUB1B, Weiss score, prognostic factors
- MeSH terms
- PTEN-Induced Putative Kinase, Adolescent, Adrenal Cortex Neoplasms, Adult, Aged, Aged, 80 and over, Diagnosis, Differential, Female, Humans, Male, Middle Aged, Neoplasm Proteins, Prospective Studies, Protein Kinases, Biomarkers, Tumor, Reproducibility of Results, Cluster Analysis, Proportional Hazards Models, Survival Analysis, Protein Serine-Threonine Kinases, Disease-Free Survival, Oligonucleotide Array Sequence Analysis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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