Dataset Information

Three-gene molecular diagnostic model for thyroid cancer.

ABSTRACT: The preoperative diagnosis of thyroid nodules primarily depends upon fine needle aspiration (FNA) cytology. However, up to 25% of FNA samples have associated "suspicious or indeterminate", but not diagnostic cytologic reports, resulting in difficulty deciding appropriate clinical management for these patients. We hypothesize that the use of molecular markers as an adjunct to FNA cytology can improve the distinction of benign from malignant nodules that have associated suspicious or indeterminate cytology.Using microarray analysis, we previously identified and reported on 75 genes useful in the distinction of benign versus malignant thyroid nodules. In the present study, we have further validated the expression of 14 of these markers in a large number of thyroid samples by immunohistochemistry (IHC) analysis of 154 thyroid tumors and quantitative real-time RT-PCR (QRT-PCR) analysis of 95 FNA samples. Of the 154 tumors analyzed by IHC, 44 samples (29%) had associated suspicious or indeterminate FNA cytology.Receiver operating characteristic using three-gene model, (HMGA2, MRC2, and SFN) analysis for the detection of malignant nodules resulted in areas under the curve (AUCs) of?0.95 (80% sensitivity; 100% specificity) and?0.84 (71% sensitivity; 84% specificity) for the IHC data in tumors, and QRT-PCR data in FNA samples, respectively.Our results suggest that a three-gene model for the cytological diagnosis of indeterminate thyroid nodules is both feasible and promising. Implementation of this as an adjunct to thyroid cytology may significantly impact the clinical management of patients with suspicious or indeterminate thyroid FNA nodules.

SUBMITTER: Prasad NB

PROVIDER: S-EPMC3286810 | biostudies-other | 2012 Mar

REPOSITORIES: biostudies-other

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Three-gene molecular diagnostic model for thyroid cancer.

Prasad Nijaguna B NB Kowalski Jeanne J Tsai Hua-Ling HL Talbot Kristin K Somervell Helina H Kouniavsky Guennadi G Wang Yongchun Y Dackiw Alan P B AP Westra William H WH Clark Douglas P DP Libutti Steven K SK Umbricht Christopher B CB Zeiger Martha A MA

Thyroid : official journal of the American Thyroid Association 20120126 3

<h4>Background</h4>The preoperative diagnosis of thyroid nodules primarily depends upon fine needle aspiration (FNA) cytology. However, up to 25% of FNA samples have associated "suspicious or indeterminate", but not diagnostic cytologic reports, resulting in difficulty deciding appropriate clinical management for these patients. We hypothesize that the use of molecular markers as an adjunct to FNA cytology can improve the distinction of benign from malignant nodules that have associated suspicio ...[more]

PMID: 22280184

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Project description:The purpose of our current study was to establish a long non-coding RNA(lncRNA) signature and assess its prognostic and diagnostic power in papillary thyroid cancer (PTC). LncRNA expression profiles were obtained from the Cancer Genome Atlas (TCGA). The key module and hub lncRNAs related to PTC were determined by weighted gene co-expression network analysis (WGCNA) and LASSO Cox regression analyses, respectively. Functional enrichment analyses, including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene set enrichment analysis were implemented to analyze the possible biological processes and signaling pathways of hub lncRNAs. Associations between key lncRNA expressions and tumor-infiltrating immune cells were identified using the TIMER website, and proportions of immune cells in high/low risk score groups were compared. Kaplan-Meier Plotter was used to evaluate the prognostic significance of hub genes in PTC. A diagnostic model was conducted with logistic regression analysis, and its diagnostic performance was assessed by calibration/receiver operating characteristic curves and principal component analysis. A nine-lncRNAs signature (SLC12A5-AS1, LINC02028, KIZ-AS1, LINC02019, LINC01877, LINC01444, LINC01176, LINC01290, and LINC00581) was established in PTC, which has significant diagnostic and prognostic power. Functional enrichment analyses elucidated the regulatory mechanism of the nine-lncRNAs signature in the development of PTC. This signature and expressions of nine hub lncRNAs were correlated with the distributions of tumor infiltrating immune cells. A diagnostic nomogram was also established for PTC. By comparing with the published models with less than or equal to nine lncRNAs, our signature showed a preferable performace for prognosis prediction. In conclusion, our present research established an innovative nine-lncRNAs signature and a six-lncRNAs nomogram that might act as a potential indicator for PTC prognosis and diagnosis, which could be conducive to the PTC treatment.

Dataset Information

Three-gene molecular diagnostic model for thyroid cancer.

Publications

Three-gene molecular diagnostic model for thyroid cancer.

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