Abstract
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.
Highlights
Clinicians are confronted with an increasing number of patients with thyroid nodules
Filtrating differentially-expressed genes in Thyroid cancer (TC) by wholetranscriptome sequence We performed whole-transcriptome sequencing of 19 paired-Papillary thyroid cancer (PTC) tissue samples to filtrate differentiallyexpressed genes
We identified a total of 212 differentiallyexpressed genes from the 19 paired-PTC tissue samples (Fig. 1), including 99 overexpressed and 113 downregulated genes, Fig. 1 Differentially expressed mRNAs in PTC tissue samples and adjacent normal tissue samples are analyzed using hierarchical clustering
Summary
Clinicians are confronted with an increasing number of patients with thyroid nodules. The number of thyroid carcinoma cases annually had increased by 4 % globally [2] and became the fastest growing type of cancer in many countries [1, 3]. China accounts for a large portion of thyroid cancer patients around the world. Accurately diagnosing thyroid nodules preoperatively is important for patients with thyroid cancer to receive timely treatment appropriately. Those with benign thyroid nodules can avoid unnecessary treatments, such as diagnostic surgery. Preoperative diagnosis of thyroid nodules can help to reduce medical burden of patients and the government to a large extent, in developing countries
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