Identification of biomarkers of adrenocortical carcinoma using genomewide gene expression profiling.
OBJECTIVE
The gene expression profiles of benign and malignant adrenocortical tumors are different.


METHODS
Genomewide gene expression profiling and validation.


METHODS
Tertiary medical center.


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


METHODS
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.


METHODS
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.


CONCLUSIONS
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.
Fernandez-Ranvier
Gustavo G
GG
Department of Surgery, J. David Gladstone Institutes Genomics Core Laboratory, University of California, San Francisco, CA 94143-1674, USA.
Weng
Julie
J
Yeh
Ru-Fang
RF
Khanafshar
Elham
E
Suh
Insoo
I
Barker
Christopher
C
Duh
Quan Yang
QY
Clark
Orlo H
OH
Kebebew
Electron
E
D000293:Adolescent; D000302:Adrenal Cortex; D000306:Adrenal Cortex Neoplasms / Q000150:complications / Q000235:genetics*; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor; D018925:Chemokines / Q000378:metabolism; D019926:Cyclin B / Q000378:metabolism; D056765:Cyclin B2; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D047748:Pituitary ACTH Hypersecretion / Q000209:etiology; D012372:ROC Curve; D044403:Receptor, Serotonin, 5-HT2B / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014408:Biomarkers, Tumor; C503758:CCNB2 protein, human; D018925:Chemokines; D019926:Cyclin B; D056765:Cyclin B2; D036341:Intercellular Signaling Peptides and Proteins; D053663:Interleukin-13 Receptor alpha2 Subunit; D027501:Monocarboxylic Acid Transporters; C478630:RARRES2 protein, human; D044403:Receptor, Serotonin, 5-HT2B