Classification of follicular cell-derived thyroid cancer by global RNA profiling

Abstract

The incidence of thyroid cancer is increasing worldwide and thyroid nodules are a frequent clinical finding. Diagnosing follicular cell-derived cancers is, however, challenging both histopathologically and especially cytopathologically. The advent of high-throughput molecular technologies has prompted many researchers to explore the transcriptome and, in recent years, also the miRNome in order to generate new molecular classifiers capable of classifying thyroid tumours more accurately than by conventional cytopathological and histopathological methods. This has led to a number of molecular classifiers that may differentiate malignant from benign thyroid nodules. Molecular classification models based on global RNA profiles from fine-needle aspirations are currently being evaluated; results are preliminary and lack validation in prospective clinical trials. There is no doubt that molecular classification will not only contribute to our biological insight but also improve clinical and pathological examinations, thus advancing thyroid tumour diagnosis and ultimately preventing superfluous surgery. This review evaluates the status of classification and biological insights gained from molecular profiling of follicular cell-derived thyroid cancers.

MicroRNA deep-sequencing reveals master regulators of follicular and papillary thyroid tumors

“…Further, the accurate diagnosis of some patients remains an unresolved challenge in the clinical setting. 4 The vast majority of thyroid tumors develop from follicular epithelial cells of the gland, often after the emergence of a driver mutation altering the MAPK pathway (affecting key genes such as BRAF, RAS, or RET). They include benign (follicular adenoma) and malignant forms (papillary thyroid carcinoma; follicular carcinoma).…”

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

“…Consequently, many patients are exposed to unnecessary surgical risk (11), requiring lifelong thyroid hormone replacement therapy and considerably increasing the healthcare burden (12). Therefore, it is paramount to identify molecular markers to aid in the diagnosis of thyroid lesions (13).…”

“…Therefore, its detection via FNAB has been proposed; however, low sensitivity is frequently seen (14). Thyroid cancer diagnostic profiles have been investigated using mRNA, miRNA, and methylation assays in tumor samples obtained from both surgical and FNAB specimens (13,15). 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.…”

miRNAs with the Potential to Distinguish Follicular Thyroid Carcinomas from Benign Follicular Thyroid Tumors: Results of a Meta-analysis

“…Despite the observation of median-based fold changes indicating diff erential expression for 7 miRNAs, t -test p-values and false discovery rates for those miRNAs were not signifi cant: p > 0.05 and FDR > 0.2 Table 2 ). The statistical testing signifi cance for the miRNA marker identifi cation could be improved in further studies with higher sample numbers or by the application of miRNA profi ling methods with higher specifi city for certain miRNA isoforms, including high-throughput sequencing [ 8 ] . Contrary to the results obtained for the previously published miRNA markers, the de novo discovery is characterized by a higher rate of cross confi rmed markers.…”