Candidate microRNAs as biomarkers of thyroid carcinoma: a systematic review, meta‐analysis, and experimental validation

Abstract

Thyroid cancer is one of the most common carcinomas of the endocrine system with an increasing incidence. A growing number of studies have focused on the diagnostic and prognostic values of dysregulated microRNAs (miRNAs) in thyroid carcinoma. However, differences in the measurement platforms, variations in lab protocols, and small sample sizes can make gene profiling data incomparable. A meta‐review of the published studies that compared miRNA expression data of thyroid carcinoma and paired normal tissues was performed to identify potential miRNA biomarkers of thyroid carcinoma with the vote‐counting strategy. Two hundred and thirty‐six aberrantly expressed miRNAs were reported in 19 microRNA expression profiling studies. Among them, 138 miRNAs were reported in at least two studies. We also provided a meta‐signature of differentially expressed miRNAs between individual histological types of thyroid carcinoma and normal tissues. The experimental validation with qRT‐PCR analysis verified that the profiles identified with the meta‐review approach could effectively discriminate papillary thyroid carcinoma tissues from paired noncancer tissues. The meta‐review of miRNA expression profiling studies of thyroid carcinoma would provide information on candidate miRNAs that could potentially be used as biomarkers in thyroid carcinoma.

Familial multinodular goiter and Sertoli-Leydig cell tumors associated with a large intragenic in-frame DICER1 deletion

“…It has been shown that let-7a and miR-345 (both 5p microRNAs) are downregulated in DICER1-related goiter, compared to normal thyroid tissue (6). Moreover, low levels of let-7 and miR-345 have been recurrently found in thyroid tumors (32,36). After the induction of hyperplasia, DICER1 'hotspot' mutations in RNase IIIb may occur on the other allele (as observed in the proband, individual I-4 and individual III-2), giving rise to cell clones that would develop into thyroid nodules.…”

CBX2 is a functional target of miRNA let‐7a and acts as a tumor promoter in osteosarcoma

“…MicroRNAs (miRNAs) are a class of extremely conserved non‐protein coding RNAs, which could regulate gene expression at a posttranscriptional level . Mounting evidence has shown that numerous miRNAs are dysregulated in tumor, contributing to the tumorigenesis and development of almost all cancer, including osteosarcoma . For instance, miR‐1 and miR‐133b were downregulated in osteosarcoma and may control cell proliferation and cell cycle .…”

Incremental utility of expanded mutation panel when used in combination with microRNA classification in indeterminate thyroid nodules

“…15,26,27 Although PIK3CA and PTEN mutations have been reported in follicular thyroid cancer, poorly differentiated thyroid cancers, and anaplastic thyroid cancer, [28][29][30] they can also be found in benign thyroid adenomas, as can GNAS and ALK mutations and THADA-and PPARG-related fusions. [46][47][48][49][50] A multiplatform approach using a combination of a mutation panel and a microRNA risk classifier has been shown to effectively "rule-in" and "rule-out" high risk of malignancy with results being predictive of surgical treatment decisions that are appropriately aligned with cancer risk. 15 Although the predictive value for malignancy of these oncogenic changes is not well understood when found individually, it is well established that coexistence of many of these oncogenic changes along with other oncogenic drivers is generally associated with aggressive forms of thyroid cancer and poor prognosis.…”