Three-Gene Molecular Diagnostic Model for Thyroid Cancer

Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

High Diagnostic Accuracy Based onCLDN10,HMGA2, andLAMB3Transcripts in Papillary Thyroid Carcinoma

“…Although a high accuracy has been demonstrated by these studies, most have failed to show optimal sensitivity and specificity in the validation analysis using independent sample sets. Molecular profiling analyses usually yield a large number of potential biomarkers; however, small sets would be more viable in clinical practice, with the use of RT-qPCR or immunohistochemistry (16).…”

Long noncoding RNA HIT000218960 promotes papillary thyroid cancer oncogenesis and tumor progression by upregulating the expression of high mobility group AT-hook 2 (HMGA2) gene

“…It has been reported that HMGA2 is overexpressed in PTC and can be used as a biomarker for distinguish- ing benign from malignant thyroid tumors. 14,15,22,25,27 The KEEG pathway analysis in this study showed that HMGA2 was enriched in the pathway of "transcriptional misregulation in cancer" .The correlation coefficient between HIT000218960 and HMGA2 was 0.999083. In addition, qRT-PCR results indicated that HIT000218960 was significantly upregulated in PTC tissues compared with noncancerous thyroid tissues, which was consistent with microarray data ( Fig.…”

The Diagnostic Utility of Combination of HMGA2 and IMP3 qRT-PCR Testing in Thyroid Neoplasms

“…11,28 A 3-gene model (HMGA2, MRC2, and SFN) was used to detect malignancy in thyroid nodules, with 71% sensitivity and 84% specificity by qRT-PCR on FNA samples. 11 Using high-dimensionality genomic analysis for molecular classification of thyroid tumors, Chudova et al 28 found a 96% NPV and 84% specificity. In our study, the HMGA2 and IMP3 combination model was analyzed to determine whether this model can increase the test sensitivity and NPV for thyroid malignancies.…”

“…3,4 Overexpression of HMGA2 was reported in a number of malignant tumors, including thyroid carcinomas. [5][6][7][8][9][10][11] In previous studies, we reported HMGA2 overexpression in thyroid malignances compared with benign lesions, using a relative quantitative reverse transcription-polymerase chain reaction (qRT-PCR) method. 7,8 IMP3 is a member of the insulin-like growth factor II mRNA-binding protein (IMP) family, which consists of IMP1, IMP2, and IMP3.…”