背景:胸腺细胞选择相关的HMG-BOX(TOX)属于一个转录因子家族,其中含有高迁移率基团盒(HMG-Box)的高度保守区域。越来越多的研究表明,TOX参与肿瘤的发生和发展,促进T细胞衰竭。我们用癌症基因组图谱(TCGA)癌症数据评估了TOX的作用。
方法:用来自TCGA和基因型-组织表达(GTEx)数据库的RNA-seq数据检测TOX表达。使用数据库分析TOX的遗传改变状态和蛋白质水平,包括人类蛋白质图谱(HPA),GeneCards,和字符串。用TCGA的生存数据估计预后意义。此外,采用R软件对TOX进行富集分析。用肿瘤免疫评估资源(TIMER)2.0数据库和“CIBERSORT”方法评估TOX与免疫细胞浸润之间的关系。进一步探讨了TOX与免疫检查点之间的相关性。免疫组织化学分析进一步验证癌组织和癌旁组织中TOX表达的差异,并且使用CCK-8测定评估细胞活力。
结果:在TCGA队列中的大多数癌症类型中,观察到差异TOX表达。检测TOX基因改变状态和蛋白水平,癌症的预后与TOX表达相关。此外,TOX水平与不同的免疫相关途径密切相关,免疫细胞浸润和免疫检查点。此外,验证了几种癌组织和癌旁组织之间TOX表达的显着差异。此外,TOX明显影响癌细胞的活力。
结论:TOX,一种潜在的癌症生物标志物,可能参与免疫微环境的调节,可用于新的靶向药物。
BACKGROUND: Thymocyte selection-associated HMG-BOX (TOX) belongs to a family of transcription factors containing a highly conserved region of the high mobility group box (HMG-Box). A growing body of research has shown that TOX is involved in the occurrence and development of tumors and promotes T-cell exhaustion. We assessed the role of
TOX with The Cancer Genome Atlas (TCGA) Pancancer Data.
METHODS: TOX expression was examined with RNA-seq data from the TCGA and Genotype-Tissue Expression (GTEx) databases. The genetic alteration status and protein level of TOX were analyzed using databases, including the Human Protein Atlas (HPA), GeneCards, and STRING. The prognostic significance was estimated with survival data from the TCGA. Moreover, R software was used for enrichment analysis of
TOX. The relationship between TOX and immune cell infiltration was assessed with the Tumor Immune Estimation Resource (TIMER) 2.0 database and the \"CIBERSORT\" method. The correlation between
TOX and immune checkpoints was further explored. Immunohistochemical analysis was used to further verify the difference in TOX expression between cancerous and paracancerous tissues, and cell viability was evaluated using a CCK-8 assay.
RESULTS: In most cancer types in the TCGA cohort, differential TOX expression was observed. The genetic alteration status and protein level of TOX were examined, and the prognosis of cancers was associated with
TOX expression. Moreover, TOX levels were closely related to different immune-related pathways, immune cell infiltration and immune checkpoints. Additionally, significant differences in TOX expression between several cancerous and paracancerous tissues were validated. Furthermore,
TOX clearly impacted the viability of cancer cells.
CONCLUSIONS: TOX, a potential biomarker for cancer, may be involved in the regulation of the immune microenvironment and can be used for new targeted drugs.