A Potential biomarker for the early diagnosis of OSCC: saliva and serum PrP(C)

用于早期诊断口腔鳞状细胞癌的潜在生物标志物:唾液和血清 PrP(C)

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Abstract

Background: Oral squamous cell carcinoma (OSCC) is frequently diagnosed at an advanced stage, and the high mortality of patients is mainly due to the delay of diagnosis. Cellular prion protein (PrP(C)) contributes to the occurrence and development of many malignant tumors. However, little has been known about the clinical and diagnostic value of PrP(C) in OSCC. This study investigated the levels of PrP(C) in the saliva and serum of patients with OSCC, OPMD and control group and their diagnostic value. Methods: The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and Clinical Proteome Tumor Analysis Consortium (CPTAC) databases were analyzed to evaluate the expression of human prion protein gene (PRNP) mRNA and PrP(C) in OSCC. Enzyme-linked Immunosorbent Assay (ELISA) was utilized to detect the expression of PrP(C) in saliva and serum samples of OSCC, OPMD and control groups. Furthermore, diagnostic value and clinical significance of PrP(C) in OSCC was identified. Protein-protein interaction (PPI) network was constructed by STRING. GO and KEGG analysis were performed by ClusterProfiler. Results: The levels of PRNP mRNA and PrP(C) in OSCC were significantly higher than those in the control group from databases (P<0.05). Besides, salivary and serum PrP(C) of OSCC patients showed increased levels compared with OPMD and control groups (P<0.05). The expression of salivary and serum PrP(C) of OSCC was correlated with the degree of differentiation (P<0.05), and the expression of PrP(C) from CPTAC was related to tumor stage of OSCC (P<0.05). The areas under the diagnostic curves (AUCs) of salivary and serum PrP(C) were 0.807 and 0.671, respectively. GO and KEGG analysis revealed that PrP(C) might be related to cell adhesion, cell differentiation, signal transduction and apoptosis, and participate in the pathways of focal adhesion, PI3K-Akt signaling pathway and ECM- receptor interaction in OSCC. Conclusion: PrP(C) in saliva and serum may be a potential biomarker for early diagnosis of OSCC.

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