Identification of genes differentially expressed in benign versus malignant thyroid tumors

Nijaguna B. Prasad, Helina Somervell, Ralph P. Tufano, Alan P B Dackiw, Michael R. Marohn, Joseph A. Califano, Yongchun Wang, William H. Westra, Douglas P. Clark, Christopher B. Umbricht, Steven K. Libutti, Martha A. Zeiger

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Purpose: Although fine-needle aspiration biopsy is the most useful diagnostic tool in evaluating a thyroid nodule, preoperative diagnosis of thyroid nodules is frequently imprecise, with up to 30% of fine-needle aspiration biopsy cytology samples reported as "suspicious" or "indeterminate." Therefore, other adjuncts, such as molecular-based diagnostic approaches are needed in the preoperative distinction of these lesions. Experimental Design: In an attempt to identify diagnostic markers for the preoperative distinction of these lesions, we chose to study by microarray analysis the eight different thyroid tumor subtypes that can present a diagnostic challenge to the clinician. Results: Our microarray-based analysis of 94 thyroid tumors identified 75 genes that are differentially expressed between benign and malignant tumor subtypes. Of these, 33 were overexpressed and 42 were underexpressed in malignant compared with benign thyroid tumors. Statistical analysis of these genes, using nearest-neighbor classification, showed a 73% sensitivity and 82% specificity in predicting malignancy. Real-time reverse transcription-PCR validation for 12 of these genes was confirmatory. Western blot and immunohistochemical analyses of one of the genes, high mobility group AT-hook 2, further validated the microarray and real-time reverse transcription - PCR data. Conclusions: Our results suggest that these 12 genes could be useful in the development of a panel of markers to differentiate benign from malignant tumors and thus serve as an important first step in solving the clinical problem associated with suspicious thyroid lesions.

Original languageEnglish (US)
Pages (from-to)3327-3337
Number of pages11
JournalClinical Cancer Research
Volume14
Issue number11
DOIs
StatePublished - Jun 1 2008
Externally publishedYes

Fingerprint

Thyroid Gland
Genes
Neoplasms
Thyroid Nodule
Microarray Analysis
Fine Needle Biopsy
Reverse Transcription
AT-Hook Motifs
Polymerase Chain Reaction
Molecular Pathology
Cell Biology
Research Design
Western Blotting
Sensitivity and Specificity

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Prasad, N. B., Somervell, H., Tufano, R. P., Dackiw, A. P. B., Marohn, M. R., Califano, J. A., ... Zeiger, M. A. (2008). Identification of genes differentially expressed in benign versus malignant thyroid tumors. Clinical Cancer Research, 14(11), 3327-3337. https://doi.org/10.1158/1078-0432.CCR-07-4495

Identification of genes differentially expressed in benign versus malignant thyroid tumors. / Prasad, Nijaguna B.; Somervell, Helina; Tufano, Ralph P.; Dackiw, Alan P B; Marohn, Michael R.; Califano, Joseph A.; Wang, Yongchun; Westra, William H.; Clark, Douglas P.; Umbricht, Christopher B.; Libutti, Steven K.; Zeiger, Martha A.

In: Clinical Cancer Research, Vol. 14, No. 11, 01.06.2008, p. 3327-3337.

Research output: Contribution to journalArticle

Prasad, NB, Somervell, H, Tufano, RP, Dackiw, APB, Marohn, MR, Califano, JA, Wang, Y, Westra, WH, Clark, DP, Umbricht, CB, Libutti, SK & Zeiger, MA 2008, 'Identification of genes differentially expressed in benign versus malignant thyroid tumors', Clinical Cancer Research, vol. 14, no. 11, pp. 3327-3337. https://doi.org/10.1158/1078-0432.CCR-07-4495
Prasad NB, Somervell H, Tufano RP, Dackiw APB, Marohn MR, Califano JA et al. Identification of genes differentially expressed in benign versus malignant thyroid tumors. Clinical Cancer Research. 2008 Jun 1;14(11):3327-3337. https://doi.org/10.1158/1078-0432.CCR-07-4495
Prasad, Nijaguna B. ; Somervell, Helina ; Tufano, Ralph P. ; Dackiw, Alan P B ; Marohn, Michael R. ; Califano, Joseph A. ; Wang, Yongchun ; Westra, William H. ; Clark, Douglas P. ; Umbricht, Christopher B. ; Libutti, Steven K. ; Zeiger, Martha A. / Identification of genes differentially expressed in benign versus malignant thyroid tumors. In: Clinical Cancer Research. 2008 ; Vol. 14, No. 11. pp. 3327-3337.
@article{c43fb652c76d488abf466d82969e6f02,
title = "Identification of genes differentially expressed in benign versus malignant thyroid tumors",
abstract = "Purpose: Although fine-needle aspiration biopsy is the most useful diagnostic tool in evaluating a thyroid nodule, preoperative diagnosis of thyroid nodules is frequently imprecise, with up to 30{\%} of fine-needle aspiration biopsy cytology samples reported as {"}suspicious{"} or {"}indeterminate.{"} Therefore, other adjuncts, such as molecular-based diagnostic approaches are needed in the preoperative distinction of these lesions. Experimental Design: In an attempt to identify diagnostic markers for the preoperative distinction of these lesions, we chose to study by microarray analysis the eight different thyroid tumor subtypes that can present a diagnostic challenge to the clinician. Results: Our microarray-based analysis of 94 thyroid tumors identified 75 genes that are differentially expressed between benign and malignant tumor subtypes. Of these, 33 were overexpressed and 42 were underexpressed in malignant compared with benign thyroid tumors. Statistical analysis of these genes, using nearest-neighbor classification, showed a 73{\%} sensitivity and 82{\%} specificity in predicting malignancy. Real-time reverse transcription-PCR validation for 12 of these genes was confirmatory. Western blot and immunohistochemical analyses of one of the genes, high mobility group AT-hook 2, further validated the microarray and real-time reverse transcription - PCR data. Conclusions: Our results suggest that these 12 genes could be useful in the development of a panel of markers to differentiate benign from malignant tumors and thus serve as an important first step in solving the clinical problem associated with suspicious thyroid lesions.",
author = "Prasad, {Nijaguna B.} and Helina Somervell and Tufano, {Ralph P.} and Dackiw, {Alan P B} and Marohn, {Michael R.} and Califano, {Joseph A.} and Yongchun Wang and Westra, {William H.} and Clark, {Douglas P.} and Umbricht, {Christopher B.} and Libutti, {Steven K.} and Zeiger, {Martha A.}",
year = "2008",
month = "6",
day = "1",
doi = "10.1158/1078-0432.CCR-07-4495",
language = "English (US)",
volume = "14",
pages = "3327--3337",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "11",

}

TY - JOUR

T1 - Identification of genes differentially expressed in benign versus malignant thyroid tumors

AU - Prasad, Nijaguna B.

AU - Somervell, Helina

AU - Tufano, Ralph P.

AU - Dackiw, Alan P B

AU - Marohn, Michael R.

AU - Califano, Joseph A.

AU - Wang, Yongchun

AU - Westra, William H.

AU - Clark, Douglas P.

AU - Umbricht, Christopher B.

AU - Libutti, Steven K.

AU - Zeiger, Martha A.

PY - 2008/6/1

Y1 - 2008/6/1

N2 - Purpose: Although fine-needle aspiration biopsy is the most useful diagnostic tool in evaluating a thyroid nodule, preoperative diagnosis of thyroid nodules is frequently imprecise, with up to 30% of fine-needle aspiration biopsy cytology samples reported as "suspicious" or "indeterminate." Therefore, other adjuncts, such as molecular-based diagnostic approaches are needed in the preoperative distinction of these lesions. Experimental Design: In an attempt to identify diagnostic markers for the preoperative distinction of these lesions, we chose to study by microarray analysis the eight different thyroid tumor subtypes that can present a diagnostic challenge to the clinician. Results: Our microarray-based analysis of 94 thyroid tumors identified 75 genes that are differentially expressed between benign and malignant tumor subtypes. Of these, 33 were overexpressed and 42 were underexpressed in malignant compared with benign thyroid tumors. Statistical analysis of these genes, using nearest-neighbor classification, showed a 73% sensitivity and 82% specificity in predicting malignancy. Real-time reverse transcription-PCR validation for 12 of these genes was confirmatory. Western blot and immunohistochemical analyses of one of the genes, high mobility group AT-hook 2, further validated the microarray and real-time reverse transcription - PCR data. Conclusions: Our results suggest that these 12 genes could be useful in the development of a panel of markers to differentiate benign from malignant tumors and thus serve as an important first step in solving the clinical problem associated with suspicious thyroid lesions.

AB - Purpose: Although fine-needle aspiration biopsy is the most useful diagnostic tool in evaluating a thyroid nodule, preoperative diagnosis of thyroid nodules is frequently imprecise, with up to 30% of fine-needle aspiration biopsy cytology samples reported as "suspicious" or "indeterminate." Therefore, other adjuncts, such as molecular-based diagnostic approaches are needed in the preoperative distinction of these lesions. Experimental Design: In an attempt to identify diagnostic markers for the preoperative distinction of these lesions, we chose to study by microarray analysis the eight different thyroid tumor subtypes that can present a diagnostic challenge to the clinician. Results: Our microarray-based analysis of 94 thyroid tumors identified 75 genes that are differentially expressed between benign and malignant tumor subtypes. Of these, 33 were overexpressed and 42 were underexpressed in malignant compared with benign thyroid tumors. Statistical analysis of these genes, using nearest-neighbor classification, showed a 73% sensitivity and 82% specificity in predicting malignancy. Real-time reverse transcription-PCR validation for 12 of these genes was confirmatory. Western blot and immunohistochemical analyses of one of the genes, high mobility group AT-hook 2, further validated the microarray and real-time reverse transcription - PCR data. Conclusions: Our results suggest that these 12 genes could be useful in the development of a panel of markers to differentiate benign from malignant tumors and thus serve as an important first step in solving the clinical problem associated with suspicious thyroid lesions.

UR - http://www.scopus.com/inward/record.url?scp=50349094446&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=50349094446&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-07-4495

DO - 10.1158/1078-0432.CCR-07-4495

M3 - Article

C2 - 18519760

AN - SCOPUS:50349094446

VL - 14

SP - 3327

EP - 3337

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 11

ER -