A six-gene model for differentiating benign from malignant thyroid tumors on the basis of gene expression

Jennifer Rosen, Mei He, Christopher Umbricht, H. Richard Alexander, Alan P B Dackiw, Martha A. Zeiger, Steven K. Libutti, Subhash Patel, Electron Kebebew, Sareh Parangi, Bhuvanesh Singh

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Background. Thyroid nodules are common; fine-needle aspirations commonly are read as indeterminate, necessitating surgery to exclude carcinoma. We developed a 6-gene array-based predictor model to diagnose benign versus malignant thyroid lesions. In this study, we verified whether quantitative reverse transcription-polymerase chain reaction (qRT-PCR) using this model reliably can differentiate benign from malignant thyroid nodules. Methods. Molecular profiles of benign (follicular adenomas, hyperplastic nodules) and malignant tumors (papillary thyroid carcinomas, follicular variants of papillary thyroid carcinomas) were analyzed using qRT-PCR from our 6-gene model (kit, Hs.296031, Hs.24183, LSM7, SYNGR2, C21orf4). The gold standard was standard pathologic criteria. A diagnosis-predictor model was built by using the training samples and was then used to predict the class of 10 additional samples analyzed as unknowns. Results. Our predictor model using 47 training samples correctly predicted 9/10 unknowns. One sample diagnosed as benign by standard histologic criteria was diagnosed as malignant by our model (sensitivity 75%; specificity, 100%; positive predictive value, 100%; negative predictive value, 85.7%). Conclusions. Molecular diagnosis with our 6-gene model can differentiate between benign and malignant thyroid tumors with high sensitivity and specificity. In combination, these genetic markers may be a reliable test to preoperatively diagnose the malignant potential of thyroid nodules.

Original languageEnglish (US)
Pages (from-to)1050-1057
Number of pages8
JournalSurgery
Volume138
Issue number6
DOIs
StatePublished - Dec 2005
Externally publishedYes

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Thyroid Nodule
Thyroid Gland
Gene Expression
Genes
Reverse Transcription
Neoplasms
Polymerase Chain Reaction
Fine Needle Biopsy
Genetic Markers
Adenoma
Carcinoma
Sensitivity and Specificity
Papillary Thyroid cancer

ASJC Scopus subject areas

  • Surgery

Cite this

Rosen, J., He, M., Umbricht, C., Alexander, H. R., Dackiw, A. P. B., Zeiger, M. A., ... Singh, B. (2005). A six-gene model for differentiating benign from malignant thyroid tumors on the basis of gene expression. Surgery, 138(6), 1050-1057. https://doi.org/10.1016/j.surg.2005.09.010

A six-gene model for differentiating benign from malignant thyroid tumors on the basis of gene expression. / Rosen, Jennifer; He, Mei; Umbricht, Christopher; Alexander, H. Richard; Dackiw, Alan P B; Zeiger, Martha A.; Libutti, Steven K.; Patel, Subhash; Kebebew, Electron; Parangi, Sareh; Singh, Bhuvanesh.

In: Surgery, Vol. 138, No. 6, 12.2005, p. 1050-1057.

Research output: Contribution to journalArticle

Rosen, J, He, M, Umbricht, C, Alexander, HR, Dackiw, APB, Zeiger, MA, Libutti, SK, Patel, S, Kebebew, E, Parangi, S & Singh, B 2005, 'A six-gene model for differentiating benign from malignant thyroid tumors on the basis of gene expression', Surgery, vol. 138, no. 6, pp. 1050-1057. https://doi.org/10.1016/j.surg.2005.09.010
Rosen, Jennifer ; He, Mei ; Umbricht, Christopher ; Alexander, H. Richard ; Dackiw, Alan P B ; Zeiger, Martha A. ; Libutti, Steven K. ; Patel, Subhash ; Kebebew, Electron ; Parangi, Sareh ; Singh, Bhuvanesh. / A six-gene model for differentiating benign from malignant thyroid tumors on the basis of gene expression. In: Surgery. 2005 ; Vol. 138, No. 6. pp. 1050-1057.
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abstract = "Background. Thyroid nodules are common; fine-needle aspirations commonly are read as indeterminate, necessitating surgery to exclude carcinoma. We developed a 6-gene array-based predictor model to diagnose benign versus malignant thyroid lesions. In this study, we verified whether quantitative reverse transcription-polymerase chain reaction (qRT-PCR) using this model reliably can differentiate benign from malignant thyroid nodules. Methods. Molecular profiles of benign (follicular adenomas, hyperplastic nodules) and malignant tumors (papillary thyroid carcinomas, follicular variants of papillary thyroid carcinomas) were analyzed using qRT-PCR from our 6-gene model (kit, Hs.296031, Hs.24183, LSM7, SYNGR2, C21orf4). The gold standard was standard pathologic criteria. A diagnosis-predictor model was built by using the training samples and was then used to predict the class of 10 additional samples analyzed as unknowns. Results. Our predictor model using 47 training samples correctly predicted 9/10 unknowns. One sample diagnosed as benign by standard histologic criteria was diagnosed as malignant by our model (sensitivity 75{\%}; specificity, 100{\%}; positive predictive value, 100{\%}; negative predictive value, 85.7{\%}). Conclusions. Molecular diagnosis with our 6-gene model can differentiate between benign and malignant thyroid tumors with high sensitivity and specificity. In combination, these genetic markers may be a reliable test to preoperatively diagnose the malignant potential of thyroid nodules.",
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AB - Background. Thyroid nodules are common; fine-needle aspirations commonly are read as indeterminate, necessitating surgery to exclude carcinoma. We developed a 6-gene array-based predictor model to diagnose benign versus malignant thyroid lesions. In this study, we verified whether quantitative reverse transcription-polymerase chain reaction (qRT-PCR) using this model reliably can differentiate benign from malignant thyroid nodules. Methods. Molecular profiles of benign (follicular adenomas, hyperplastic nodules) and malignant tumors (papillary thyroid carcinomas, follicular variants of papillary thyroid carcinomas) were analyzed using qRT-PCR from our 6-gene model (kit, Hs.296031, Hs.24183, LSM7, SYNGR2, C21orf4). The gold standard was standard pathologic criteria. A diagnosis-predictor model was built by using the training samples and was then used to predict the class of 10 additional samples analyzed as unknowns. Results. Our predictor model using 47 training samples correctly predicted 9/10 unknowns. One sample diagnosed as benign by standard histologic criteria was diagnosed as malignant by our model (sensitivity 75%; specificity, 100%; positive predictive value, 100%; negative predictive value, 85.7%). Conclusions. Molecular diagnosis with our 6-gene model can differentiate between benign and malignant thyroid tumors with high sensitivity and specificity. In combination, these genetic markers may be a reliable test to preoperatively diagnose the malignant potential of thyroid nodules.

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