Identification of biomarkers of adrenocortical carcinoma using genomewide gene expression profiling

Arch Surg. 2008 Sep;143(9):841-6; discussion 846. doi: 10.1001/archsurg.143.9.841.

Abstract

Hypothesis: The gene expression profiles of benign and malignant adrenocortical tumors are different.

Design: Genomewide gene expression profiling and validation.

Setting: Tertiary medical center.

Patients: Eighty-five patients with benign adrenocortical tumors (n = 74) and adrenocortical carcinoma (n = 11).

Intervention: Real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) in 89 adrenocortical tissue samples (11 malignant and 78 benign). The criteria for differentially expressed genes between benign and malignant adrenocortical tumors were a false discovery rate of less than 5% and an adjusted P < .01. Genes differentially expressed by 8-fold higher or lower were validated by RT-PCR.

Main outcome measures: The diagnostic accuracy of differentially expressed genes as determined by the area under the receiver operating characteristic curve (AUC).

Results: We found 37 genes differentially expressed by 8-fold higher or lower. Fifteen genes were downregulated and 22 were upregulated in adrenocortical carcinoma. Of the 37 genes, 29 differentially expressed by microarray correlated with the gene expression levels by quantitative RT-PCR (P < or = .01). Of the 37 genes validated by RT-PCR, 22 were significantly differentially expressed between benign and malignant adrenocortical tumors (P < .05). Five of these 22 genes had an AUC of 0.80 or greater (the AUC for IL13RA2 was 0.90; HTR2B, 0.87; CCNB2, 0.86; RARRES2, 0.86; and SLC16A9, 0.80), indicating high diagnostic accuracy for distinguishing benign from malignant adrenocortical tumors.

Conclusion: We identified 37 genes that are dysregulated in adrenocortical carcinoma, and several of the differentially expressed genes have excellent diagnostic accuracy for distinguishing benign from malignant adrenocortical tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenal Cortex
  • Adrenal Cortex Neoplasms / complications
  • Adrenal Cortex Neoplasms / genetics*
  • Adult
  • Aged
  • Area Under Curve
  • Biomarkers, Tumor*
  • Chemokines / metabolism
  • Cyclin B / metabolism
  • Cyclin B2
  • Female
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-13 Receptor alpha2 Subunit / metabolism
  • Male
  • Middle Aged
  • Monocarboxylic Acid Transporters / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Pituitary ACTH Hypersecretion / etiology
  • ROC Curve
  • Receptor, Serotonin, 5-HT2B / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Biomarkers, Tumor
  • CCNB2 protein, human
  • Chemokines
  • Cyclin B
  • Cyclin B2
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-13 Receptor alpha2 Subunit
  • Monocarboxylic Acid Transporters
  • RARRES2 protein, human
  • Receptor, Serotonin, 5-HT2B