Analysis And Validation Of The Role And Mechanism Of PDL1 In Oral Cancer Based On Bioinformatics Databases

Objective:This study preliminarily predicts the clinical significance and immune regulatory role of PDL1 in head and HNSCC based on the TCGA database;Secondly,the effects of PDL1 on the proliferation,migration,and invasion of Cal27 and SCC25 cells were studied at the cell level in vitro;Finally,based on the GEO database,the molecular mechanism of PDL1 regulating the development of oral cancer was elucidated and further validated,aiming to provide new ideas for the prevention and treatment of oral cancer.Methods:In this study,we first used the gene expression profile and clinical data of HNSCC patients in the TCGA database to analyze the correlation between PDL1 expression and survival prognosis and clinical pathological indicators of patients.We used immune infiltration and immunocyte analysis to study the relationship between PDL1 expression and tumor microenvironment(TME).We analyzed the biological function and enrichment signal pathway of PDL1 through PPI protein network interaction,GO and KEGG enrichment;Secondly,the expression level of PDL1 in different oral cancer cells was studied at the cell level in vitro.The effects of low expression of PDL1 on the proliferation,migration,and invasion of oral cancer cells were studied using CCK8,colony formation,and Transwell experiments;Finally,the oral cancer dataset from the GEO database was used to screen for differentially expressed genes that affect PDL1expression and differentially expressed genes that affect lymph node metastasis.The intersection of the two was used to obtain potential genes that PDL1 regulates oral cancer metastasis.The PPI network of PDL1 and potential genes was constructed using the String database,and the key genes that PDL1 regulates the network were screened.Analyze the correlation between PDL1 and key genes using the gene expression profile of HNSCC patients,analyze the potential molecular mechanisms of PDL1 and key genes using the KEGG database,and further validate the impact of low PDL1 expression on key genes at the in vitro cell level.ResultsThis study first analyzed based on the TCGA database and found that PDL1 was significantly overexpressed in HNSCC patients.Survival analysis showed that the survival time of HNSCC patients decreased over time.Clinical indicator analysis showed a significant correlation between PDL1 and lymph node metastasis.Immune infiltration analysis showed that PDL1 expression significantly affected the three immune infiltration scores.Immune cell analysis showed that PDL1 expression significantly affected the proportion of CD4~+T cells,CD8~+T cells,and M1 type macrophages,The results of PDL1 protein network interaction analysis,GO analysis,and KEGG pathway analysis showed that PDL1 mainly functions through the PD1/PDL1 signaling pathway in human diseases,and the main genes enriched in this pathway are CD247,CD3E,CD4,PDCD1,and PTPN11.Secondly,the results of this study at the cellular level showed that PDL1 was significantly overexpressed in different oral cancer cell lines,and low expression of PDL1 could inhibit the proliferation,migration,invasion,and other cellular biological behaviors of oral cancer cell lines Cal27 and SCC25.Finally,using the GEO database analysis,a total of 48 intersection genes that simultaneously regulate PDL1 and tumor metastasis in oral cancer were obtained.PPI protein network interaction analysis showed that PDL1 and intersection genes STAT1,CXCL9,and CXCL10 were constructed as direct network nodes.At the same time,based on the analysis of HNSCC gene expression profile data in the TCGA database,it was found that PDL1 was positively correlated with STAT1,CXCL9,and CXCL10 expression,And it was found that inhibiting PDL1 expression significantly reduced STAT1,CXCL9,and CXCL10 levels in oral cancer cell lines Cal27 and SCC25.Further analysis of KEGG pathway enrichment revealed that PDL1 can promote the growth and metastasis of oral cancer cells by activating the Jak/STAT signaling pathway,thereby regulating the expression of STAT1,CXCL9,and CXCL10.Similarly,this study found that inhibiting the Jak/STAT signaling pathway in oral cancer cell lines Cal27 and SCC25 can further inhibit the impact of low PDL1expression on the proliferation,migration,and invasion of oral cancer,and reduce the expression of STAT1,CXCL9,and CXCL10.Conclusions:PDL1 is highly expressed in HNSCC and affects lymph node metastasis.The differential expression of PDL1 can affect the proportion of CD4~+T,CD8~+T,and M1 type macrophages in TME to regulate the level of HNSCC immune infiltration.PDL1 is overexpressed in oral cancer,while low expression of PDL1 can inhibit cancer cell proliferation,migration,and invasion.PDL1 can promote the metastasis of oral cancer cells by activating the Jak/STAT signaling pathway and regulating the expression of STAT1,CXCL9,and CXCL10.