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Salivary IL-6 mRNA is a Robust Biomarker in Oral Squamous Cell Carcinoma.

ABSTRACT: Salivary IL-6 mRNA was previously identified as a promising biomarker of oral squamous cell carcinoma (OSCC). We performed a multi-center investigation covering all geographic areas of Hungary. Saliva from 95 patients with OSCC and 80 controls, all Caucasian, were collected together with demographic and clinicopathological data. Salivary IL-6 mRNA was quantified by real-time quantitative PCR. Salivary IL-6 protein concentration was measured by enzyme-linked immune-sorbent assay. IL-6 protein expression in tumor samples was investigated by immunohistochemistry. Normalized salivary IL-6 mRNA expression values were significantly higher (p < 0.001) in patients with OSCC (mean ± SE: 3.301 ± 0.885) vs. controls (mean ± SE: 0.037 ± 0.012). Differences remained significant regardless of tumor stage and grade. AUC of the ROC curve was 0.9379 (p < 0.001; 95% confidence interval: 0.8973-0.9795; sensitivity: 0.945; specificity: 0.819). Salivary IL-6 protein levels were significantly higher (p < 0.001) in patients (mean ± SE: 70.98 ± 14.06 pg/mL), than in controls (mean ± SE: 12.45 ± 3.29). Specificity and sensitivity of IL-6 protein were less favorable than that of IL-6 mRNA. Salivary IL-6 mRNA expression was significantly associated with age and dental status. IL-6 manifestation was detected in tumor cells and tumor-infiltrating leukocytes, suggesting the presence of a paracrine loop of stimulation. Salivary IL-6 mRNA is one of the best performing and clinically relevant biomarkers of OSCC.

SUBMITTER: Marton IJ

PROVIDER: S-EPMC6912409 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Salivary IL-6 mRNA is a Robust Biomarker in Oral Squamous Cell Carcinoma.

Márton Ildikó Judit IJ Horváth József J Lábiscsák Péter P Márkus Bernadett B Dezső Balázs B Szabó Adrienn A Tar Ildikó I Piffkó József J Jakus Petra P Barabás József J Barabás Péter P Olasz Lajos L Kövér Zsanett Z Tőzsér József J Sándor János J Csősz Éva É Scholtz Beáta B Kiss Csongor C

Journal of clinical medicine 20191113 11

Salivary IL-6 mRNA was previously identified as a promising biomarker of oral squamous cell carcinoma (OSCC). We performed a multi-center investigation covering all geographic areas of Hungary. Saliva from 95 patients with OSCC and 80 controls, all Caucasian, were collected together with demographic and clinicopathological data. Salivary IL-6 mRNA was quantified by real-time quantitative PCR. Salivary IL-6 protein concentration was measured by enzyme-linked immune-sorbent assay. IL-6 protein exp ...[more]

PMID: 31766212

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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.

Dataset Information

Salivary IL-6 mRNA is a Robust Biomarker in Oral Squamous Cell Carcinoma.

Publications

Salivary IL-6 mRNA is a Robust Biomarker in Oral Squamous Cell Carcinoma.

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