MicroRNAs MiR-218, MiR-125b, and Let-7g Predict Prognosis in Patients with Oral Cavity Squamous Cell Carcinoma (original) (raw)
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microRNAs expression predicts local recurrence risk in oral squamous cell carcinoma
Head & neck, 2014
Background: Oral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide with a high rate of recurrence. MicroRNAs (miRNAs) are gene regulators playing an important role in oral carcinogenesis. We aimed to identify and functionally characterize miRNAs that predict recurrence in OSCC. Methods: We collected 92 OSCC with their normal tissue counterparts and we performed miRNAs expression profiling on 74 OSCC and 38 normal tissues. The association between the expression of microRNAs and clinical outcome was evaluated in 69 followed-up patients. Results: Four of the miRNAs deregulated between OSCC and normal tissues. areprognostic for recurrence either when considered individually or as a group. Depletion of the expression of prognostic miRNAs inhibits the proliferation of OSCC cells Conclusions: MicroRNAs are differentially expressed in OSCC versus normal samples. The expression of 4 prognostic microRNAs signature is able to predict recurrence risk independently from ot...
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...
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.
Head & Neck
Background: For early-stage oral squamous cell carcinoma (OSCC), there is no existing risk-stratification modality beyond conventional TNM staging system to identify patients at high risk for cancer-specific mortality. Methods: A total of 568 early-stage OSCC patients who had surgery only and also with available 5-year clinical outcomes data were identified. Signature microRNAs (miRNAs) were discovered using deep sequencing analysis and validated by qRT-PCR. The final 5-plex prognostic marker panel was utilized to generate a cancer-specific mortality risk score using the multivariate Cox regression analyses. The prognostic markers were validated in the internal and external validation cohorts. Results: The risk score from the 5-plex marker panel consisting of miRNAs-127-3p, 4736, 655-3p, TNM stage and histologic grading stratified patients into four risk categories. Compared to the low-risk group, the high-risk group had 23-fold increased mortality risk (hazard ratio 23, 95% confidence interval
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...
2010
micrornas (mirnas) mir15a and let7a are important regulators of bcl-2, ras and c-myc proteins. considering that these mirnas are commonly altered in many human cancers and that these proteins are reported to be altered in oral squamous cell carcinoma (OScc), we investigated them in a set of OScc cases. the mirnas as well as the proteins were evaluated in the tumor and blood of 20 patients by real-time quantitative pcr and immunohistochemistry, respectively. the expression of mir15a and bcl-2 proteins in the tumors was not associated with each other or with tumor staging. On the other hand, we found reduced expression of this mirna in the blood of patients with an advanced stage of OScc and with lymph node metastasis. the expression of let7a in the tumor and blood was not associated with tumor size, lymph node metastasis, tumor staging and immunoexpression of ras and c-myc proteins. in conclusion, the present study shows that reduced expression of mir15a is associated with OScc staging.
The American Journal of Pathology, 2009
Small noncoding microRNAs (miRNAs) have been shown to be abnormally expressed in every tumor type examined. The importance of miRNAs as potential cancer prognostic indicators is underscored by their involvement in the regulation of basic cellular processes such as cell proliferation, differentiation, and apoptosis. In this study, miRNA expression profiles of head and neck squamous cell carcinoma (HNSCC) tumor and adjacent normal tissue were examined by microarray analysis and validated by quantitative TaqMan real-time polymerase chain reaction. Using TaqMan real-time polymerase chain reaction we measured the quantitative associations between a subset of miRNAs identified on microarrays in primary tumors at diagnosis and cancer survival in a cohort of 104 HNSCC patients undergoing treatment with curative intent. The majority of miRNAs exhibiting altered expression in primary human HNSCC tumors show lower expression levels relative to normal adjacent tissue. In contrast, hsa-miR-21 is frequently overexpressed in human HNSCC tumors. Using univariate and multivariable statistical models we show that low levels of hsa-miR205 are significantly associated with loco-regional recurrence independent of disease severity at diagnosis and treatment. In addition , combined low levels of hsa-miR-205 and hsa-let-7d expression in HNSCC tumors are significantly associated with poor head and neck can-cer survival Our results show that miRNA expression levels can be used as prognostic markers of head and neck cancer.
Current Issues in Molecular Biology
Oral squamous cell carcinoma (OSCC) is considered the sixth most common cancer worldwide. To reduce the high mortality of the disease, sensitive and specific diagnostic and prognostic biomarkers are urgently needed. Non-coding RNA, microRNAs (miRNAs), which are short length non-coding transcripts, or long non-coding RNA (lncRNA) seem to be potential biomarkers, considering that they have an important role in regulation of cell fate being involved in a wide range of biological processes. Literature data emphasized the important role of these transcripts as a biomarker for diagnosis and prognosis in oral squamous cell carcinoma. Therefore, we have evaluated the expression levels of a panel of four miRNAs (miR-21-5p, miR-93-5p, miR-200c-3p and miR-205-5p) and H19, MALAT1 by quantitative real-time PCR (qRT-PCR) from 33 fresh frozen tissues and 33 normal adjacent tissues. Our date revealed miR-21-5p and miR-93-5p to be upregulated, while miR-200c-3p and miR-205-5p to be downregulated. Re...
Journal of Oncology
We have previously constructed a novel microRNA (miRNA)-based prognostic model and cancer-specific mortality risk score formula to predict survival outcome in oral squamous cell carcinoma (OSCC) patients who are already categorized into “early-stage” by the TNM staging system. A total of 836 early-stage OSCC patients were assigned the mortality risk scores. We evaluated the efficacy of various treatment regimens in terms of survival benefit compared to surgery only in patients stratified into high (risk score ≥0) versus low (risk score <0) mortality risk categories. For the high-risk group, surgery with neck dissection significantly improved the 5-year survival to 75% from 46% with surgery only ( p < 0.001 ); a Cox proportional hazard model on time-to-death demonstrated a hazard ratio of 0.37 for surgery with neck dissection (95% CI: 0.2–0.6; p = 0.0005 ). For the low-risk group, surgery only was the treatment of choice associated with 5-year survival benefit. Regardless of tr...
MicroRNA profile in the squamous cell carcinoma: prognostic and diagnostic roles
Heliyon, 2020
Head and neck squamous cell carcinomas (HNSCCs) are human malignancies associated with both genetic and environmental factors. MicroRNAs (miRNAs) as a group of small non-coding RNAs have prominent roles in the development of this kind of cancer. Expressions of several miRNAs have been demonstrated to be increased in HNSCC samples vs. non-malignant tissues. In silico prediction tools and functional analyses have confirmed the function of some miRNAs in the modulation of cancer-associated targets, thus indicating these miRNAs as onco-miRs. Moreover, numerous miRNAs have been down-regulated in HNSCC samples. Their targets mostly enhance cell proliferation or inhibit apoptosis. miRNAs signature has practical implications in the diagnosis, staging, and management of HNSC. Most notably, numerous miRNAs have been shown to alter response of tumor cells to anticancer drugs such as cisplatin and doxorubicin. Circulating levels of these small transcripts have been suggested as promising biomarkers for diagnosis of HNSCC. In the present manuscript, we sum up the available literature regarding the miRNAs signature in HNSCC and their role as diagnostic/prognostic biomarkers.