目的 研究胸苷酸合酶(thymidylate synthase,TYMS)与甲状腺乳头状癌(thyroid papillary carcinoma,PTC)的相关性,并探讨相关机制.方法 通过TIMER 2.0 数据库分析TYMS在癌症中的表达;TCGA等数据库中分析TYMS在甲状腺癌中表达;应用免疫组化检测PTC组织和对应的癌旁组织TYMS蛋白表达;使用Kaplan-Meier绘图仪和ROC曲线评估TYMS与预后的关系;采用基因本体功能注释(gene ontology,GO)、京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路分析和基因富集分析(gene set enrichment analysis,GSEA)预测TYMS的生物学作用;通过TIMER等工具探讨TYMS对肿瘤浸润免疫细胞(tumor-infiltrating immune cells,TIICs)的潜在作用.结果 TYMS在 18种癌症中高表达(P<0.05);甲状腺癌组织中TYMS表达上调(P<0.05),TYMS高表达与甲状腺癌患者预后不良相关(P<0.05);免疫组化中,PTC中TYMS为高表达;靶基因GO和KEGG分析主要与细胞因子与受体相互作用有关,GSEA分析主要与中性粒细胞脱颗粒、细胞外基质调节、趋化因子信号通路有关;TYMS表达可影响甲状腺癌中多种免疫细胞的浸润水平(P<0.05).结论 TYMS在PTC组织中呈现高表达,且与不良预后和免疫浸润相关,TYMS有望成为PTC诊断和免疫治疗的新靶点.
Correlation Between TYMS and Thyroid Cancer and Its Potential Mechanism
Objective To study the correlation between thymidine synthase(TYMS)and thyroid papillary carcinoma(PTC),and to explore the related mechanism.Methods The expression of TYMS in cancer was analyzed by TIMER 2.0 database.The ex-pression of TYMS in thyroid cancer was analyzed in TCGA and other databases.TYMS protein expression in PTC tissues and corre-sponding paracancer tissues was detected by immunohistochemistry.Kaplan-Meier plotter and ROC curve were used to evaluate the re-lationship between TYMS and prognosis.Gene Ontology GO Functional Annotation,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis and Gene Set Enrichment Analysis(GSEA)were used to predict the biological role of TYMS.The poten-tial effect of TYMS on tumor infiltrating immune cells(TIICs)was investigated using TIMER and other tools.Results TYMS was highly expressed in 18 cancers(P<0.05).The expression of TYMS in thyroid cancer tissues was up-regulated(P<0.05),and high expression of TYMS was associated with poor prognosis in thyroid cancer patients(P<0.05).In immunohistochemistry,TYMS were highly expressed in PTC.Target gene GO and KEGG analysis were mainly related to the interaction between cytokines and receptors,while GSEA analysis was mainly related to neutrophil degranulation,extracellular matrix regulation and chemokine signaling pathway.TYMS expression could affect the infiltration level of multiple immune cells in thyroid carcinoma(P<0.05).Conclusion TYMS showed high expression in PTC tissues,and was associated with poor prognosis and immune infiltration.TYMS is expected to become a new target for PTC diagnosis and immunotherapy.
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