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Expression Of PES1 In Head And Neck Squamous Cell Carcinoma And Its Correlation With Immune Infiltration

Posted on:2024-05-23Degree:MasterType:Thesis
Country:ChinaCandidate:Y D HeFull Text:PDF
GTID:2544307082966159Subject:Oral and clinical medicine
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Background: PES1 is a nucleolar protein responsible for the processing of ribosomal pre-RNA.According to recent findings,PES1 is expressed at noticeably higher levels in the tissues of a number of malignancies,which aids in the invasion and growth of cancer and serves as a cancer promoter.Its thorough study will assist offer a theoretical foundation for early identification and treatment of head and neck squamous carcinoma(HNSCC),although the expression level and biological role of PES1 in HNSCC are unclear.Methods: Downloading and collecting the HNSCC dataset from The Cancer Genome Atlas(TCGA)and GEO databases,along with a q RT-PCR assay,enables the analysis of PES1 m RNA expression in both normal oral epithelial tissue and tumor tissue of HNSCC patients.Based on the UALCAN and Kaplan-Meier databases,the correlation of PES1 m RNA expression levels with clinicopathological characteristics and patient prognosis was assessed.Univariate and multifactorial COX regression analyses revealed whether PES1 was an independent risk factor for HNSCC.Functional enrichment analysis can reveal the involvement and role of PES1 in tumor-related biology.x CELL,TIMER,TIDE,and other technologies were used to predict the link between PES1 m RNA expression and tumor immune cell infiltration and immunotherapy response.QRT-PCR and Western blotting revealed PES1 m RNA and protein expression in five HNSCC cell lines: HN4,HN6,SCC4,SCC9 and CAL27.HNSCC cell lines with silenced PES1 expression were constructed.By using the CCK-8 assay and the plate colony formation assay,in vitro experiments were conducted to determine the impact of suppressing PES1 expression on the capacity of HNSCC cells to proliferate.Following the development of a subcutaneous xenograft tumor model in nude mice,it was investigated how changing PES1 expression affected the capacity of HNSCC cells to proliferate in vivo.Scratch healing and other assays were used to observe whether PES1 expression had an effect on the migration and invasion of HNSCC cells.Results: PES1 m RNA expression levels in HNSCC tissues were significantly higher than those in normal oral epithelial tissues,according to the results of TCGA and GEO database analysis and q RT-PCR,and PES1 expression was closely correlated with HPV status,tumor stage,clinical grade and TP53 mutation status.PES1 is believed to be a reliable biological indicator and is regarded as a legitimate biomarker that can aid in the improved identification and prediction of the overall survival of HNSCC patients.Gene enrichment analysis showed that in HNSCC,PES1 is mainly involved in signaling pathways such as immunoglobulin complexes,antigen binding,T cell receptors,B cell receptors and Toll-like receptor signaling pathways.Meanwhile,predictions based on the TIDE algorithm supported that patients with high PES1 expression responded better to immunotherapy.q RT-PCR and Western blot assays both showed that PES1 expression was higher in HNSCC cell lines HN4,HN6,SCC4,SCC9,and CAL27 than in normal oral epithelial cells.A stable HNSCC cell line with suppressed PES1 expression that prevents SCC9 and CAL27 cells from proliferating,migrating,and invading was successfully screened.Conclusion: PES1 is significantly overexpressed in HNSCC tissues and is associated not only with tumor stage,clinical grade and survival prognosis,but also with immune infiltration and immunotherapeutic response of HNSCC.PES1 is expected to be a novel molecular target for the detection,prognosis,and therapy of HNSCC since it decreases the proliferation,migration,and invasive capacity of HNSCC cells when its expression is silenced.
Keywords/Search Tags:PES1, tumor immune microenvironment, prognosis, TCGA, head and neck squamous cell carcinoma
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