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Meta-Analysis and Meta-Review of Thyroid Cancer Gene Expression Profiling Studies Identifies Important Diagnostic Biomarkers

Obi L. Griffith, Adrienne Melck, Steven J.M. Jones, Sam M. Wiseman

From the Michael Smith Genome Sciences Centre, British Columbia Cancer Agency; Departments of Medical Genetics and Surgery, University of British Columbia; Genetic Pathology Evaluation Center, Prostate Research Center of Vancouver General Hospital & British Columbia Cancer Agency; Department of Surgery, St Paul's Hospital, Vancouver, Canada

Address reprint requests to Sam M. Wiseman, MD, FRCSC, FACS, St Paul's Hospital, Room C302 Burrard Bldg, 1081 Burrard Street, Vancouver, BC, V6Z1Y6, Canada; smwiseman{at}providencehealth.bc.ca

Purpose: An estimated 4% to 7% of the population will develop a clinically significant thyroid nodule during their lifetime. In many cases, preoperative diagnoses by needle biopsy are inconclusive. Thus, there is a clear need for improved diagnostic tests to distinguish malignant from benign thyroid tumors. The recent development of high-throughput molecular analytic techniques should allow the rapid evaluation of new diagnostic markers. However, researchers are faced with an overwhelming number of potential markers from numerous thyroid cancer expression profiling studies.

Materials and Methods: To address this challenge, we have carried out a comprehensive meta-review of thyroid cancer biomarkers from 21 published studies. A gene ranking system that considers the number of comparisons in agreement, total number of samples, average fold-change and direction of change was devised.

Results: We have observed that genes are consistently reported by multiple studies at a highly significant rate (P < .05). Comparison with a meta-analysis of studies reprocessed from raw data showed strong concordance with our method.

Conclusion: Our approach represents a useful method for identifying consistent gene expression markers when raw data are unavailable. A review of the top 12 candidates revealed well known thyroid cancer markers such as MET, TFF3, SERPINA1, TIMP1, FN1, and TPO as well as relatively novel or uncharacterized genes such as TGFA, QPCT, CRABP1, FCGBP, EPS8 and PROS1. These candidates should help to develop a panel of markers with sufficient sensitivity and specificity for the diagnosis of thyroid tumors in a clinical setting.

Supported by the BC Cancer Foundation. Canadian Institutes of Health Research (O.L.G), the Natural Sciences and Engineering Council of Canada, and the Michael Smith Foundation for Health Research (S.J.M.J. and S.M.W.).

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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