Abstract
Objective: To clear the expression of transcription factor Dickkopf-1 (DKK1) in Oral Squamous Cell Carcinoma (OSCC) using the method of bioinformatics analysis. And to clarify the relationship between the expression of DKK1 and the clinicopathological characteristics of OSCC using the method of molecular biology and cytobiology, in order to determine the early diagnosis and significance of OSCC according to the marker of DKK1. Methods: In this study, the expression level of DKK1 in OSCC tissues was analyzed using GEPIA and TCGA databases, and then verified in vitro by qRTPCR and Western-blot analysis. The correlation between DKK1 gene expression and the clinical pathological parameters of OSCC, and also the impact of DKK1 on prognosis were determined using the LinkedOmics database. In addition, DKK1 was knocked down by RNA interference in SCC-4 and SCC-25 OSCC cell lines and the proliferation ability of OSCC cells was assessed by MTT assay. Results: High expression of DKK1 in OSCC is positively correlated with the pathological grade and T stage of OSCC. According to the TCGA results, DKK1 mRNA was highly expressed and it is related to the overall survival rate of OSCC. In addition, the expression level of both DKK1mRNA and protein were significantly raised in the cell line SCC-25 and SCC-4. Furthermore, MTT analysis showed that DKK1 knockdown resulted in reduced proliferation of OSCC cells. Conclusions: TCGA database analysis showed that DKK1 was highly expressed in OSCC, and it is closely correlated to the pathological parameters of OSCC, which will provide important theoretical guidance for the subsequent study of oral squamous cell carcinoma.
Highlights
To investigate the expression of transcription factor Dickkopf-1 (DKK1) in oral squamous cell carcinomas (OSCC) by bioinformatics analysis and to clarify the connection between expression of DKK1 and clinicopathological features of OSCC, so as to elucidate the early diagnosis and prognostic significance of OSCC by DKK1
The TCGA database analysis found that DKK1 is highly expressed in OSCC and is associated with multiple pathological indicators of OSCC, which will provide important theoretical guidance for subsequent oral squamous cell carcinoma research
3.1 DKK1 mRNA was highly expressed in OSCC and normal oral epithelial tissues GEPIA database was used to analyze the expression of DKK1 in different tumors, and the results showed that the expression level of DKK1 was increased in most tumors, such as esophageal cancer, squamous cell carcinoma, pancreatic adenocarcinoma, etc., including head and neck squamous cell carcinoma (Figure 1).The expression of DKK1 mRNA in OSCC (n=519) and normal head and neck epithelial tissue (n=44) was further analyzed
Summary
To investigate the expression of transcription factor Dickkopf-1 (DKK1) in oral squamous cell carcinomas (OSCC) by bioinformatics analysis and to clarify the connection between expression of DKK1 and clinicopathological features of OSCC, so as to elucidate the early diagnosis and prognostic significance of OSCC by DKK1. In chronic lymphocytic leukemia (CLL) it is expressed at normal levels, but unable to affect Wnt/β-catenin pathway, while in multiple myeloma, DKK1's role is shown to change from tumor suppressor to a stress responsive gene involved in the JNK pathway [15, 16]. As all these studies have shown, the activity and expression levels of DKK1 varies in different cancers. The role of DKK1 in oral squamous cell carcinoma was analyzed through the database website and verified by Quantitative real-time PCR and Western-blot analysis, so as to provide a theoretical basis for determining whether its mechanism and possible use as a predictive marker for the prognosis of OSCC patients
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