Whole-transcriptome profiling of thyroid nodules identifies expression-based signatures for accurate thyroid cancer diagnosis.
OBJECTIVE
Due to the limitations of fine-needle aspiration biopsy (FNAB) cytopathology, many individuals who present with thyroid nodules eventually undergo thyroid surgery to diagnose thyroid cancer. The objective of this study was to use whole-transcriptome profiling to develop and validate a genomic classifier that significantly improves the accuracy of preoperative thyroid cancer diagnosis.


METHODS
Nucleic acids were extracted and amplified for microarray expression analysis on the Affymetrix Human Exon 1.0 ST GeneChips from 1-mm-diameter formalin-fixed and paraffin-embedded thyroid tumor tissue cores. A training group of 60 thyroidectomy specimens (30 cancers and 30 benign lesions) were used to assess differential expression and for subsequent generation of a genomic classifier. The classifier was validated in a blinded fashion on a group of 31 formalin-fixed and paraffin-embedded thyroid FNAB specimens.


RESULTS
Expression profiles of the 57 thyroidectomy training and 31 FNAB validation specimens that passed a series of quality control steps were analyzed. A genomic classifier composed of 249 markers that corresponded to 154 genes, had an overall validated accuracy of 90.0% in the 31 patient FNAB specimens and had positive and negative predictive values of 100% and 85.7%, respectively. The majority of the identified markers that made up the classifier represented non-protein-encoding RNAs.


CONCLUSIONS
Whole-transcriptome profiling of thyroid nodule surgical specimens allowed for the development of a genomic classifier that improved the accuracy of preoperative thyroid cancer FNAB diagnosis.
Bsc, MD, FRCSC, Room C303, Burrard Building, Department of Surgery, St Paul's Hospital, 1081 Burrard Street, Vancouver, British Columbia, Canada V6Z 1Y6. smwiseman@providencehealth.bc.ca.
Sam M
SM
Wiseman
Zaid
Z
Haddad
Blair
B
Walker
Ismael A
IA
Vergara
Thomas
T
Sierocinski
Anamaria
A
Crisan
Mercedeh
M
Ghadessi
Phuong
P
Dao
Benedikt
B
Zimmermann
Timothy J
TJ
Triche
Nicholas
N
Erho
Elai
E
Davicioni
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044963:Biopsy, Fine-Needle; D003937:Diagnosis, Differential; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D013961:Thyroid Gland / Q000473:pathology* / Q000601:surgery; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D016606:Thyroid Nodule / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D059467:Transcriptome