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Circulating microRNA Panel as a Potential Novel Biomarker for Oral Squamous Cell Carcinoma Diagnosis.

ABSTRACT: A lack of reliable biomarkers for oral squamous cell carcinoma (OSCC) poses a major clinical issue. The sensitivity and specificity of classical serum tumor markers, such as the squamous cell carcinoma antigen (SCC-Ag), are quite poor, especially for early detection. This study aimed to identify specific serum miRNAs potentially serving as OSCC biomarkers. The expression levels of candidate miRNAs in serum samples from 40 OSCC patients and 40 healthy controls were quantitatively analyzed via microarray and reverse transcription PCR (RT-PCR) analyses. To enhance the accuracy of detection, we used Fisher's linear discriminant analysis to establish a diagnostic model that incorporated a combination of selected miRNAs. Consequently, miR-19a and miR-20a were significantly upregulated in the patient group (p = 0.014 and 0.036, respectively), whereas miR-5100 was downregulated (p = 0.001). We found that a combination of six miRNAs (miR-24, miR-20a, miR-122, miR-150, miR-4419a, and miR-5100) could distinguish between OSCC and the control group with a higher degree of accuracy (Area Under the Curve, AUC: 0.844, sensitivity: 55%, and specificity: 92.5%). Furthermore, compared to serum SCC antigen, the 6-miRNA panel could accurately detect the presence of OSCC. The present specific miRNAs panel may serve as a novel candidate biomarker of oral cancer.

SUBMITTER: Nakamura K

PROVIDER: S-EPMC7865311 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Circulating microRNA Panel as a Potential Novel Biomarker for Oral Squamous Cell Carcinoma Diagnosis.

Nakamura Kodai K Hiyake Naomi N Hamada Tomofumi T Yokoyama Seiya S Mori Kazuki K Yamashiro Kouta K Beppu Mahiro M Sagara Yasuaki Y Sagara Yoshiaki Y Sugiura Tsuyoshi T

Cancers 20210125 3

A lack of reliable biomarkers for oral squamous cell carcinoma (OSCC) poses a major clinical issue. The sensitivity and specificity of classical serum tumor markers, such as the squamous cell carcinoma antigen (SCC-Ag), are quite poor, especially for early detection. This study aimed to identify specific serum miRNAs potentially serving as OSCC biomarkers. The expression levels of candidate miRNAs in serum samples from 40 OSCC patients and 40 healthy controls were quantitatively analyzed via mic ...[more]

PMID: 33504017

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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.

Project description:BACKGROUND:MicroRNA (miR)s are promising diagnostic biomarkers of cancer. Recent next generation sequencer (NGS) studies have found that isoforms of micro RNA (isomiR) circulate in the bloodstream similarly to mature micro RNA (miR). We hypothesized that combination of circulating miR and isomiRs detected by NGS are potentially powerful cancer biomarker. The present study aimed to investigate their application in esophageal cancer. METHODS:Serum samples from patients with esophageal squamous cell carcinoma (ESCC) and age and sex matched healthy control (HC) individuals were investigated for the expression of miR/isomiRs using NGS. Candidate miR/isomiRs which met the criteria in the 1st group (ESCC = 18 and HC = 12) were validated in the 2nd group (ESCC = 30 and HC = 30). A diagnostic panel was generated using miR/isomiRs that were consistently confirmed in the 1st and 2nd groups. Accuracy of the panel was tested then in the 3rd group (ESCC = 18 and HC = 18). Their use was also investigated in 22 paired samples obtained pre- and post-treatment, and in patients with esophageal adenocarcinoma (EAD) and high-grade dysplasia (HGD). RESULTS:Twenty-four miR/isomiRs met the criteria for diagnostic biomarker in the 1st and 2nd group. A multiple regression model selected one mature miR (miR-30a-5p) and two isomiRs (isoform of miR-574-3p and miR-205-5p). The index calculated from the diagnostic panel was significantly higher in ESCC patients than in the HCs (13.3±8.9 vs. 3.1±1.3, p<0.001). The area under the receiver operating characteristics (ROC) curves of the panel index was 0.95. Sensitivity and specificity were 93.8%, and 81% in the 1st and 2nd groups, and 88.9% and 72.3% in the 3rd group, respectively. The panel index was significantly lower in patients with EAD (6.2±4.5) and HGD (4.2±1.7) than in those with ESCC and was significantly decreased at post-treatment compared with pre-treatment (6.2±5.6 vs 11.6±11.5, p = 0.03). CONCLUSION:Our diagnostic panel had high accuracy in the diagnosis of ESCC. MiR/isomiRs detected by NGS could serve as novel biomarkers of ESCC.

Dataset Information

Circulating microRNA Panel as a Potential Novel Biomarker for Oral Squamous Cell Carcinoma Diagnosis.

Publications

Circulating microRNA Panel as a Potential Novel Biomarker for Oral Squamous Cell Carcinoma Diagnosis.

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