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

Barros-Filho, Mateus Camargo; Marchi, Fábio Albuquerque; Pinto, Clóvis Antônio Lopes; Rogatto, Sílvia Regina; Kowalski, Luiz Paulo

doi:10.1210/jc.2014-4053

Cited by 47 publications

(45 citation statements)

References 41 publications

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“…Chiappetta et al reported that the mRNA expression of HMGA2 is associated with malignant phenotype in human thyroid neoplasias [44]. HMGA2 was also used as a diagnostic marker in previous studies [14, 45]. In our study, HMGA2 was significantly upregulated in primary TC tissue, compared with benign and normal thyroid nodules.…”

Section: Discussionsupporting

confidence: 64%

“…Another panel, named ThyroSeq v2 assay, which consists of more than 50 gene mutations and gene fusions (more than 1,000 hotspots), performed with 90 % sensitivity, 93 % specificity, 83 % PPV, and 96 % NPV by using next-generation sequence [8]. Other studies also achieved encouraging effects [14–19]. However, these diagnostic panels are too complex and costly to apply in clinical practice.…”

Section: Discussionmentioning

confidence: 99%

“…Another panel, named ThyroSeq v2 assay, which consists of more than 50 gene mutations and gene fusions (more than 1,000 hotspots), makes accurate diagnosis with 90 % sensitivity, 93 % specificity, 83 % positive predictive value (PPV), and 96 % negative predictive value (NPV) by using next-generation sequence [8]. Other studies also performed with impressive PPV or NPV [14–17]. Nevertheless, studies aforementioned have their limitations.…”

Section: Introductionmentioning

confidence: 99%

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A panel of four genes accurately differentiates benign from malignant thyroid nodules

Wang

Chen

Cai

et al. 2016

J Exp Clin Cancer Res

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BackgroundClinicians are confronted with an increasing number of patients with thyroid nodules. Reliable preoperative diagnosis of thyroid nodules remains a challenge because of inconclusive cytological examination of fine-needle aspiration biopsies. Although molecular analysis of thyroid tissue has shown promise as a diagnostic tool in recent years, it has not been successfully applied in routine clinical use, particularly in Chinese patients.MethodsWhole-transcriptome sequencing of 19 primary papillary thyroid cancer (PTC) samples and matched adjacent normal thyroid tissue (NT) samples were performed. Bioinformatics analysis was carried out to identify candidate diagnostic genes. Then, RT-qPCR was performed to evaluate these candidate genes, and four genes were finally selected. Based on these four genes, diagnostic algorithm was developed (training set: 100 thyroid cancer (TC) and 65 benign thyroid lesions (BTL)) and validated (independent set: 123 TC and 81 BTL) using the support vector machine (SVM) approach.ResultsWe discovered four genes, namely fibronectin 1 (FN1), gamma-aminobutyric acid type A receptor beta 2 subunit (GABRB2), neuronal guanine nucleotide exchange factor (NGEF) and high-mobility group AT-hook 2 (HMGA2). A SVM model with these four genes performed with 97.0 % sensitivity, 93.8 % specificity, 96.0 % positive predictive value (PPV), and 95.3 % negative predictive value (NPV) in training set. For additional independent validation, it also showed good performance (92.7 % sensitivity, 90.1 % specificity, 93.4 % PPV, and 89.0 % NPV).ConclusionsOur diagnostic panel can accurately distinguish benign from malignant thyroid nodules using a simple and affordable method, which may have daily clinical application in the near future.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-016-0447-3) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A panel of four genes accurately differentiates benign from malignant thyroid nodules

Wang

Chen

Cai

et al. 2016

J Exp Clin Cancer Res

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“…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.…”

Section: Identification Of Lncrna-hit000218960 Potentially Associatedmentioning

confidence: 62%

“…The reported studies on the association between HMGA2 and clinicopathological features mostly focused on the diagnostic utility of HMGA2 to distinguish between benign and malignant thyroid tumors. [21][22][23][24][25][26] In other malignancies, such as nasopharyngeal carcinoma, high HMGA2 expression is correlated with N stage, 2-year metastasis status and poor survival prognosis. 27,28 The correlation between HIT000218960 expression and clinicopathological features observed in our study was consistent with that of HMGA2.…”

Section: Discussionmentioning

confidence: 99%

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

Yang

et al. 2016

Cell Cycle

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Accumulating evidence suggests that long noncoding RNAs (lncRNAs) play an important role in oncogenesis and tumor progression. However, our knowledge of lncRNAs in thyroid cancer is still limited. To explore the crucial lncRNAs involved in oncogenesis of papillary thyroid cancer (PTC), we acquired data of differentially expressed lncRNAs between PTC tissues and paired adjacent noncancerous thyroid tissues through lncRNA microarray. In the microarray data, we observed that a newly identified lncRNA, HIT000218960, was significantly upregulated in PTC tissues and associated with a well-known oncogene, high mobility group AT-hook 2 (HMGA2) gene. Both in normal thyroid tissues and PTC tissues, the expression of HIT000218960 was significantly positively correlated with that of HMGA2 mRNA. Knockdown of HIT000218960 in PTC cells resulted in downregulation of HMGA2. In addition, functional assays indicated that inhibition of HIT000218960 in PTC cells suppressed cell proliferation, colony formation, migration and invasion in vitro. Increased HIT000218960 expression in PTC tissues was obviously correlated with lymph node metastasis and multifocality, as well as TNM stage. Those findings suggest that HIT000218960 might acts as a tumor promoter through regulating the expression of HMGA2.

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Increased gene expression of TIMP1 and CHI3L1 in fine‐needle aspiration biopsy samples from papillary thyroid cancer as compared to benign nodules

Dimitrova

Shinkov

Dodova

et al. 2021

Diagnostic Cytopathology

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Background Thyroid nodules are common ultrasound findings with malignancy rate 7%–15%. Our objective was to assess the relative expression of the tissue inhibitor of metalloproteinase‐1 gene (TIMP1) and chitinase‐3‐like protein 1 gene (CHI3L1) in fine‐needle aspiration biopsy (FNAB) washouts and the serum levels of their protein products (TIMP‐1 and chitinase‐3‐like protein 1 known as YKL‐40) in patients with papillary thyroid cancer (PTC) and patients with benign nodules. Furthermore, the correlation between gene expression and circulating protein product was evaluated. Methods Eighty patients who underwent FNAB in one tertiary center were recruited in the study. Forty with Bethesda V and VI nodules were operated and PTC was confirmed. The other 40 patients were with Bethesda II nodules. TIMP‐1 and YKL‐40 serum levels were measured in all subjects. The TIMP1 and CHI3L1 expression was assessed in FNAB washouts from 20 PTC patients and 20 benign cases using quantitative PCR. Results The relative expression of TIMP1 and CHI3L1 was significantly higher in the PTC group than in the benign group (p < .001 for TIMP1; p = .018 for CHI3L1). The PTC patients had higher serum TIMP‐1 than the patients with benign nodules (p = .036). We did not find significant difference in the YKL‐40 level between the two groups. TIMP1 and CHI3L1 expression did not correlate with the serum levels of their protein products. Conclusion FNAB washouts could be used for identification of diagnostic markers. The increased TIMP1 and CHI3L1 expression implies a role of these genes in the PTC carcinogenesis.

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

Abstract: A promising tool with high performance for PTC diagnosis based on three transcripts was designed with the potential to predict lymph node metastasis risk.

Cited by 47 publications

References 41 publications

A panel of four genes accurately differentiates benign from malignant thyroid nodules

A panel of four genes accurately differentiates benign from malignant thyroid nodules

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

Increased gene expression of TIMP1 and CHI3L1 in fine‐needle aspiration biopsy samples from papillary thyroid cancer as compared to benign nodules

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