microRNAs expression predicts local recurrence risk in oral squamous cell carcinoma (original) (raw)
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Scientific Reports
Oral squamous cell carcinoma (OSCC), the most common type of head and neck cancers, is associated with high recurrence, metastasis, low long-term survival rates and poor treatment outcome. As deregulated miRNA expression plays a crucial role in malignant transformation and cancer progression, the present study is aimed at profiling the miRNA expression pattern in OSCC and developing a new miRNA prognostic signature for oral cancer. MiRNA expression profiling was performed using MiRNA microarray in 30 tumor and 18 normal samples. MiRNA signature obtained was validated with quantitative real time PCR (qRT-PCR) in 144 tumor and 36 normal samples. The potential targets, clinical implications and prognostic value of the miRNA signature were elucidated by various bioinformatics and statistical analyses. Microarray profiling identified a set of 105 miRNAs to be differentially expressed in OSCC, out of which a subset of 19 most dysregulated miRNAs were validated by qRT-PCR. In silico analys...
The differential regulation of microRNAs is associated with oral cancer
Oncology reports, 2017
Oral squamous cell carcinoma (OSCC), is the most frequently occurring malignant head and neck tumor, generally it exhibits a poor prognosis, and metastasis is the main cause of death in these cancer patients. The discovery of reliable prognostic indicators for tumors progression would greatly improve clinical treatments. MicroRNAs (miRNAs) play a critical role in the degradation of mRNA and the inhibition of protein synthesis. The miRNAs function either as tumor suppressors or as oncogenes in tumorigenesis, and little is known about the clinical significance of miRNA expression profiles in oral cancers. In the present study, we investigated the expression profiles of miR-375, miR-204 and miR-196a in 39 healthy and tumor tissue pairs of oral cancer patients using TaqMan real-time quantitative polymerase chain reaction (qPCR). The predicted target genes for miR-375, miR-204 and miR-196a were confirmed using luciferase reporter-based assays and western blot analyses. In oral cancer tis...
PLoS ONE, 2014
MicroRNAs (miRNAs) have a major impact on regulatory networks in human carcinogenesis. In this study, we sought to investigate the prognostic significance of miRNAs in patients with oral cavity squamous cell carcinoma (OSCC). In a discovery phase, RNA was extracted from 58 OSCC tumor samples and paired normal tissues. MiRNAs expression was evaluated with TaqMan Array Card and TaqMan MicroRNA assays. The prognostic significance of the miRNA signature identified in the discovery phase was validated by qRT-PCR in a replication set consisting of 141 formalin-fixed, paraffinembedded (FFPE) samples. We identified a miRNA regulatory network centered on the three hub genes (SP1, MYC, and TP53) that predicted distinct clinical endpoints. Three miRNAs (miR-218, miR-125b, and let-7g) and their downstream response genes had a concordant prognostic significance on disease-free survival and disease-specific survival rates. In addition, patients with a reduced expression of miR-218, miR-125b, and let-7g have a higher risk of poor outcomes in presence of specific risk factors (p-stage III-IV, pT3-4, or pN+). Our findings indicate that specific miRNAs have prognostic significance in OSCC patients and may improve prognostic stratification over traditional risk factors. (TCY) . These authors contributed equally to this work.
MicroRNAs as Important Players and Biomarkers in Oral Carcinogenesis
BioMed research international, 2015
Oral cancer, represented mainly by oral squamous cell carcinoma (OSCC), is the eighth most common type of human cancer worldwide. The number of new OSCC cases is increasing worldwide, especially in the low-income countries, and the prognosis remains poor in spite of recent advances in the diagnostic and therapeutic modalities. MicroRNAs (miRNAs), 18-25 nucleotides long noncoding RNA molecules, have recently gained significant attention as potential regulators and biomarkers for carcinogenesis. Recent data show that several miRNAs are deregulated in OSCC, and they have either a tumor suppressive or an oncogenic role in oral carcinogenesis. This review summarizes current knowledge on the role of miRNAs as tumor promotors or tumor suppressors in OSCC development and discusses their potential value as diagnostic and prognostic markers in OSCC.
Circulating miRNAs as biomarkers for oral squamous cell carcinoma recurrence in operated patients
Oncotarget, 2016
MicroRNAs (miRNAs) are small regulatory non-coding RNAs for which altered expression in cancers can serve as potential biomarkers for diseases. We here investigated whether circulating miRNAs can serve as biomarkers for predicting post-operational recurrence of oral squamous cell carcinoma (OSCC) in patients. Plasma samples from 8 Danish OSCC patients were collected before, and one year after surgical operation, as well as from 3 Danish healthy controls and subjected to miRNA profiling by next generation sequencing. Disease recurrence did not occur in the 8 patients when the post-operative plasma samples were collected. Based on the sequencing data, three up-regulated miRNAs (miR-148a-3p, miR-26a-5p and miR-21-5p) and three down-regulated miRNAs (miR-375, miR-92b-3p and miR-486-5p) in the OSCC samples compared to healthy controls were selected for qRT-PCR validation in a Chinese cohort of 20 plasma samples collected before, and 9-12 months after surgical operation, and 18 healthy co...
miRNA expression profiles of oral squamous cell carcinomas
Anticancer research, 2013
Oral squamous cell carcinoma (OSCC) development involves complex machinery of genomic and epigenetic regulations including microRNA (miRNA) expression changes. We aimed to analyze the expression patterns of a set of miRNAs in human TNM stage I and II OSCC samples in an autologous normal mucosa-controlled experimental design. Forty samples of OSCC and 40 matched normal tissues were evaluated for miR-21, miR-155, miR-191, miR-146a, miR-221 and miR-222 expression in a LightCycler 480(PCR) system. Our results showed significant overexpression of miR-21, miR-155, miR-191 and miR-221 in paired-sample t-test and the sensitivity/specificity of tests were over 90% in the case of miR-21 and miR-155 on the receiver operating characteristic curve (ROC) analysis. Our results underline the role of miR-21 in OSCC and support the possible causal role of miR-155 and miR-221 in oral carcinogenesis. The overexpression of miR-191 is a novel finding in squamous cell carcinoma.
A panel of microRNAs can be used to determine oral squamous cell carcinoma
Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology, 2017
Subjective histopathology is currently used to diagnose oral squamous cell carcinoma (OSCC). We tested if abundances of a panel of microRNA could be an objective OSCC indicator. Literature review enabled identification of 10 microRNAs associated with oral and head and neck malignancies. We extracted RNA from formalin-fixed paraffin embedded biopsies; 20 each with OSCC, dysplasia or histologically normal epithelium (HNE) and 10 with oral lichen planus (OLP). Relative abundances of microRNAs in HNE and OSCC were determined using reverse transcription then real time PCR with global mean normalization. MicroRNAs differentially expressed (test microRNA, T-miR) and non-differentially expressed (normalization microRNA, N-miR) were identified. The raw microRNA Cq data was incorporated in a developed algorithm that output a T-miR expression value (T-miREV) score. Raw Cq data from HNE, OSCC, dysplasia and OLP samples were then used to test the algorithm scoring and OSCC classification. Four t...
Journal of Oral Pathology & Medicine, 2019
More than 90% of the malignancies in the oral cavity are belonged to oral squamous cell carcinoma (OSCC) which is characterized by spreading to the cervical lymph nodes. 1 Molecular studies have demonstrated novel biomarkers for evaluation in diagnostic, therapeutic, and prognostic levels to improve survival rate of patients of OSCC especially in early stages. 2,3 The expression patterns of miR-NAs (miRs) in oral squamous cell carcinoma represent new directions in the search of oral carcinogenesis. 4 Although there are many studies about miRs in serum, plasma and urine in different type of carcinomas such as OSCC, but circulating miRs, may play an important role as diagnostic or prognostic biomarkers in human carcinomas. 5 Also recently, circulating miRs have been described as biomarkers for head and neck cancers in multiple anatomical sites including the skin, the oral cavity, nasopharynx, larynx, and salivary glands. 6 The miRs are small, single-stranded, non-coding RNA molecules that program many intracellular processes including cell differentiation,
Oncogenic microRNAs as biomarkers of oral tumorigenesis and minimal residual disease
Objectives: Classical diagnostic methods are not sensitive enough in detecting oral lesions that may progress to cancer and in assessing minimal residual disease (MRD) in oral surgical margins. Altered expression of microRNAs (miRNAs) contributes to human cancer, including oral cancer. Although there are many studies on microRNAs in oral cancer, there is no reported study comparing the expression of microRNAs during oral tumor progression and in oral surgical margins. Materials and methods: This study analyzed the expression of 72 miRNAs that were reported (till June 2011) to be differentially expressed in oral cancer, during phases of oral cancer progression and in oral surgical margins. Results: Of the 72 miRNAs analyzed, four (hsa-miR-125a, hsa-miR-184, hsa-miR16 and hsa-miR-96) showed a common pattern of expression in both sets of tissues. We further analyzed the downstream target genes of hsa-miR-16 BCL2 and CCND1. The in silico network analysis of these four microRNAs and their target genes revealed presence of genes involved in tumor progression and transcription factors. Conclusions: The findings suggest that the combinatorial regulation by these miRNAs and their target transcription factors might play a substantial role in oral tumorigenesis. Here we report for the first time that a decreased expression of hsa-miR-125a, hsa-miR-184 and hsa-miR-16 and an increased expression of hsa-miR-96 could be useful in predicting oral tumorigenesis and importantly in the detection of MRD and decision-making process for postoperative treatment modalities.