MicroRNA expression profiling is a potential diagnostic tool for thyroid cancer

Abstract

BACKGROUND: Approximately 30% of fine‐needle aspiration (FNA) biopsies of thyroid nodules are indeterminate or nondiagnostic. Recent studies suggest microRNA (miRNA, miR) is differentially expressed in malignant tumors and may have a role in carcinogenesis, including thyroid cancer. The authors therefore tested the hypothesis that miRNA expression analysis would identify putative markers that could distinguish benign from malignant thyroid neoplasms that are often indeterminate on FNA biopsy. METHODS: A miRNA array was used to identify differentially expressed genes (5‐fold higher or lower) in pooled normal, malignant, and benign thyroid tissue samples. Real‐time quantitative polymerase chain reaction was used to confirm miRNA array expression data in 104 tissue samples (7 normal thyroid, 14 hyperplastic nodule, 12 follicular variant of papillary thyroid cancer, 8 papillary thyroid cancer, 15 follicular adenoma, 12 follicular carcinoma, 12 Hurthle cell adenoma, 20 Hurthle cell carcinoma, and 4 anaplastic carcinoma cases), and 125 indeterminate clinical FNA samples. The diagnostic accuracy of differentially expressed genes was determined by analyzing receiver operating characteristics. RESULTS: Ten miRNAs showed >5‐fold expression difference between benign and malignant thyroid neoplasms on miRNA array analysis. Four of the 10 miRNAs were validated to be significantly differentially expressed between benign and malignant thyroid neoplasms by quantitative polymerase chain reaction (P < .002): miR‐100, miR‐125b, miR‐138, and miR‐768‐3p were overexpressed in malignant samples of follicular origin (P < .001), and in Hurthle cell carcinoma samples alone (P < .01). Only miR‐125b was significantly overexpressed in follicular carcinoma samples (P < .05). The accuracy for distinguishing benign from malignant thyroid neoplasms was 79% overall, 98% for Hurthle cell neoplasms, and 71% for follicular neoplasms. The miR‐138 was overexpressed in the FNA samples (P = .04) that were malignant on final pathology with an accuracy of 75%. CONCLUSIONS: MicroRNA expression differs for normal, benign, and malignant thyroid tissue. Expression analysis of differentially expressed miRNA could help distinguish benign from malignant thyroid neoplasms that are indeterminate on thyroid FNA biopsy. Cancer 2011. © 2011 American Cancer Society.

MiR-125b promotes cell migration and invasion by targeting PPP1CA-Rb signal pathways in gastric cancer, resulting in a poor prognosis

“…The expression of MiR-125b in cancers is controversial. Some studies have shown that MiR-125b is upregulated or downregulated in different cancers under pathophysiological conditions [16][17][18][19]. Although our previous study reported that MiR-125b was upregulated 4.88-fold in gastric cancer [20], the expression level and biological impact of MiR-125b in gastric cancer were never well studied.…”

miR-125a inhibits the migration and invasion of liver cancer cells via suppression of the PI3K/AKT/mTOR signaling pathway

“…Ascertaining the origin and development of liver cancer and identification of novel targets for therapy have been the focus of recent studies regarding HCC (3)(4)(5)(6)(7). MicroRNAs (miRs) are single-stranded noncoding RNAs, containing 17-19 nucleotides, which are associated with the development and progression of tumors (8)(9)(10)(11)(12) such as oropharyngeal squamous cell carcinoma (8), non-small cell lung cancer (9), thyroid cancer (10). miR-125a has previously been reported to block the proliferation, invasion and migration of breast cancer cells (13), and was also found to be effective in preventing the invasion of ovarian cancer (14), glioma (15), lung cancer (16)(17)(18) and gastric cancer (19).…”

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

“…The results did not comprise a merging of the expression levels of all the evaluated miRNAs, which may have improved the diagnostic potential. Along the same vein, a comprehensive study by Vriens et al (2012) (miR-100, miR-125b, miR-138 and miR-768-3p were up-regulated in the malignant entities). Subsequent QRT-PCR analysis of the specific miRNAs revealed miR-138 to be differentially expressed between benign and malignant FNAs (P!0.001) and an ultimate diagnostic accuracy of 75% and NPV of 81%.…”