关键词: TYMP bioinformatics analysis ccRCC immune regulation nomogram

Mesh : Humans Prognosis Carcinoma, Renal Cell / diagnosis genetics Thymidine Phosphorylase Biomarkers Carcinoma Kidney Neoplasms / diagnosis genetics

来  源:   DOI:10.1177/15330338231194555   PDF(Pubmed)

Abstract:
In clear cell renal cell carcinoma (ccRCC), only some patients can benefit from immunotherapy therapy, and it is urgent to find immune-related molecular markers and targets.
Thymidine phosphorylase (TYMP) expression level and predictive value in pan-cancers were analyzed using TIMER, GEPIA2, and The Human Protein Atlas. We obtained ccRCC tissues to verify the differential expression of TYMP and confirmed the biological function in vitro. Subsequently, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) are used to explore the potential mechanism of TYMP. Finally, TIMER was used to analyze the infiltration levels and prognostic value of different immune cells.
TYMP is upregulated in various cancers, including ccRCC, and there is a certain degree of causality between high expression and poor prognosis in ccRCC. It was confirmed that TYMP knockdown could suppress cell aggressiveness, and cause cell death. Differential analysis showed that 55 differential genes were upregulated in the high-expression groups of TYMP. KEGG and GSEA analyses suggested that TYMP was linked to immune cell invasion, fatty acid metabolism, and P53 signaling pathway. Further investigation revealed that the expression level of TYMP linked positively to T-cell follicular helper and Tregs, but negatively with mast cell activation. Finally, a Nomogram was established on the base of expression level of TYMP and the clinical characteristics of ccRCC patients to predict prognosis.
Patient survival is poor and immune cell infiltration is abnormal when TYMP is highly expressed in ccRCC, suggesting that ccRCC patients could benefit from using TYMP as a molecular diagnostic and therapeutic target.
摘要:
背景:在透明细胞肾细胞癌(ccRCC)中,只有一些患者可以从免疫治疗中受益,迫切需要找到与免疫相关的分子标志物和靶点。
方法:使用TIMER分析全癌症中胸苷磷酸化酶(TYMP)的表达水平和预测价值,GEPIA2和人类蛋白质图谱。我们获得了ccRCC组织以验证TYMP的差异表达,并在体外证实了其生物学功能。随后,基因本体论,京都基因和基因组百科全书(KEGG),和基因集富集分析(GSEA)用于探索TYMP的潜在机制。最后,TIMER用于分析不同免疫细胞的浸润水平和预后价值。
结果:TYMP在各种癌症中上调,包括ccRCC,ccRCC高表达与预后不良之间存在一定的因果关系。证实了TYMP敲低可以抑制细胞侵袭性,并导致细胞死亡。差异分析表明,在TYMP的高表达组中,有55个差异基因上调。KEGG和GSEA分析表明,TYMP与免疫细胞侵袭有关,脂肪酸代谢,和P53信号通路。进一步的研究表明,TYMP的表达水平与T细胞滤泡辅助细胞和Tregs呈正相关,但与肥大细胞激活呈阴性。最后,a根据TYMP的表达水平和ccRCC患者的临床特征建立列线图以预测预后。
结论:当TYMP在ccRCC中高表达时,患者生存率较差,免疫细胞浸润异常,提示ccRCC患者可受益于使用TYMP作为分子诊断和治疗靶点。
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