Dataset Information

Salivary miR-30c-5p as Potential Biomarker for Detection of Oral Squamous Cell Carcinoma.

ABSTRACT: The levels of different classes of extracellular RNAs (exRNAs) remain stable in bodily fluids. The detection of either enriched or depleted specific subsets of salivary microRNAs (miRNAs) has the potential to serve as a non-invasive approach for biomarker development. Thus, salivary miRNAs have emerged as a promising molecular tool for early diagnosis and screening of oral squamous cell carcinoma (OSCC). Total RNA was extracted from saliva supernatant of 33 OSCC patients and 12 controls (discovery set), and the differential expression of 8 cancer-related miRNAs was detected by TaqMan assay. Among the screened miRNAs, miR-30c-5p (p < 0.04) was significantly decreased in OSCC saliva. The same transcriptional behavior of miR30c-5p was observed in an additional validation set. miR-30c-5p showed a significant statistical difference between cases and controls with areas under the curve (AUC) of 0.82 (95% CI: 0.71-0.89). The sensitivity and the specificity of miR-30c-5p were 86% and 74%, respectively. The target identification analysis revealed enrichment of miR-30c-5p targets in p53 and Wnt signaling pathways in OSCC. Additionally, the miR-30c-5p targets had clinical significance related to overall survival. In conclusion, these findings show that downregulated miR-30c-5p has the potential to serve as a novel, non-invasive biomarker for early OSCC detection.

SUBMITTER: Mehterov N

PROVIDER: S-EPMC8465705 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Salivary miR-30c-5p as Potential Biomarker for Detection of Oral Squamous Cell Carcinoma.

Mehterov Nikolay N Vladimirov Boyan B Sacconi Andrea A Pulito Claudio C Rucinski Marcin M Blandino Giovanni G Sarafian Victoria V

Biomedicines 20210824 9

The levels of different classes of extracellular RNAs (exRNAs) remain stable in bodily fluids. The detection of either enriched or depleted specific subsets of salivary microRNAs (miRNAs) has the potential to serve as a non-invasive approach for biomarker development. Thus, salivary miRNAs have emerged as a promising molecular tool for early diagnosis and screening of oral squamous cell carcinoma (OSCC). Total RNA was extracted from saliva supernatant of 33 OSCC patients and 12 controls (discove ...[more]

PMID: 34572265

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Project description:Survival rates of oral squamous cell carcinoma (OSCC) remained substantially unchanged over the last decades; thus, additional prognostic tools are strongly needed. Salivary miRNAs have emerged as excellent non-invasive cancer biomarker candidates, but their association with OSCC prognosis has not been investigated yet. In this study, we analyzed global salivary miRNA expression in OSCC patients and healthy controls, with the aim to define its diagnostic and prognostic potential. Methods: Saliva was collected from patients with newly diagnosed untreated primary OSCC and healthy controls. Global profiling of salivary miRNAs was carried out through a microarray approach, while signature validation was performed by quantitative real-time PCR (RT-qPCR). A stringent statistical approach for microarray and RT-qPCR data normalization was applied. The diagnostic performance of miRNAs and their correlation with OSCC prognosis were comprehensively analyzed. Results: In total, 25 miRNAs emerged as differentially expressed between OSCC patients and healthy controls and, among them, seven were significantly associated with disease-free survival (DFS). miR-106b-5p, miR-423-5p and miR-193b-3p were expressed at high levels in saliva of OSCC patients and their combination displays the best diagnostic performance (ROC - AUC = 0.98). Moreover, high expression of miR-423-5p was an independent predictor of poor DFS, when included in multivariate survival analysis with the number of positive lymph nodes - the only significant clinical prognosticator. Finally, we observed a significant decrease in miR-423-5p expression in matched post-operative saliva samples, suggesting its potential cancer-specific origin. Conclusion: Salivary miRNAs identified in our cohort of patients show to be accurate in OSCC detection and to effectively stratify patients according to their likelihood of relapse. These results, if validated in an independent set of patients, could be particularly promising for screening/follow-up of high-risk populations and useful for preoperative prognostic assessment.

Project description:BackgroundNeuropilin-2 (NRP2) is a single chain transmembrane glycoprotein that acts as a co-receptor of VEGF and is related to the pathogenesis of various tumors closely. However, the clinical significance of NRP2 in oral squamous cell carcinoma (OSCC) is unclear.PurposeThe objective of this study was to investigate the role of NRP2 in the pathogenesis of OSCC and explore the associated mechanisms.Materials and methodsGEPIA (gene expression profiling interactive analysis) was used to analyze the expression of NRP2 in OSCC. Immunohistochemistry and RT-qPCR were used to detect NRP2 expression in 80 OSCC samples. The clinical correlations and prognostic significance of NRP2 expression were evaluated. In addition, the biological functions of OSCC cells transfected with shNRP2 were evaluated. The expression levels of β-catenin, C-myc, cyclin D1, and MMP-2 in Wnt/β-catenin signaling pathway were assessed by RT-qPCR after inhibiting the expression of NRP2 in SCC-25 cell line.ResultsAnalysis of cases using GEPIA revealed that NRP2 was substantially upregulated in OSCC. NRP2 expression was also significantly higher in our OSCC samples than in the controls. Elevated expression of NRP2 was correlated with lymph node metastasis (P<0.01) and distant metastasis (P<0.05) in OSCC patients, and high NRP2 levels, lymph node metastasis, and distant metastasis were associated with poor prognosis (Kaplan-Meier analysis; P<0.05). Univariate and multivariate Cox analysis showed that lymph node metastasis, distant metastasis, and NRP2 expression were independent risk factors for overall survival (OS) and disease-free survival (DFS) in OSCC patients (P<0.05). Furthermore, the proliferation, migration, and invasion of OSCC cells were inhibited by shNRP2. Following inhibiting of NRP2 expression in the SCC-25 cell line, the expression levels of β-catenin, C-myc, cyclin D1, and MMP-2 were reduced (P<0.05).ConclusionThis study shows that NRP2 functions as a tumor promoter gene in OSCC by affecting the proliferation, migration, and invasion of OSCC cells and downregulating the Wnt/β-catenin pathway. These results highlight the potential role for NRP2 as a clinical diagnostic marker.

Dataset Information

Salivary miR-30c-5p as Potential Biomarker for Detection of Oral Squamous Cell Carcinoma.

Publications

Salivary miR-30c-5p as Potential Biomarker for Detection of Oral Squamous Cell Carcinoma.

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