Pan-cancer analysis of N4-acetylcytidine adaptor THUMPD1 as a predictor for prognosis and immunotherapy.
Pan-cancer analysis of N4-acetylcytidine adaptor THUMPD1 as a predictor for prognosis and immunotherapy.
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DOI：
10.1042/bsr20212300
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发表时间：
2021-12-22
影响因子：
4
通讯作者：
Zhu X
中科院分区：
文献类型：
--
作者：
Li K;Liu J;Yang X;Tu Z;Huang K;Zhu X
背景：THUMPD1是一种特异的RNA接头，可协助mRNA的乙酰化和n4 -乙酰胞苷（ac4C）的产生。然而，尚不清楚THUMPD1是否在肿瘤发生和治疗效果中起作用。在此，我们分析了THUMPD1在泛癌中的表达谱和预后价值，并深入了解了THUMPD1表达水平与免疫治疗效果的相关性。方法：从基因型-组织表达（GTEx）、Cancer cell Line Encyclopedia （CCLE）和The Cancer Genome Atlas （TCGA）数据库中获取泛癌组织中基因表达模式及其与预后、免疫细胞浸润的相关性，采用Kaplan-Meier法和Spearman相关分析。对临床样品进行免疫印迹和免疫荧光来验证我们的数据库衍生结果。基于接受程序性细胞死亡蛋白1配体（PD-L1）抗体治疗的临床队列，还探讨了THUMPD1表达水平与免疫治疗反应的相关性。最后，进行基因集富集分析（GSEA）以揭示可能的致瘤机制。结果：THUMPD1在大多数癌症类型中高表达，这种表达升高预示着不同癌症的预后不良或改善。在肾透明细胞癌（KIRC）和直肠腺癌（READ）中，THUMPD1高表达的患者预后较好，而肝肝细胞癌（LIHC）患者预后较差。此外，在许多癌症类型中，THUMPD1与免疫细胞浸润、肿瘤突变负荷（TMB）、微卫星不稳定性（MSI）、免疫检查点和新抗原显著相关。此外，在THUMPD1高表达的患者中观察到更多的临床优势和治疗效果。结论：THUMPD1可作为评价不同类型肿瘤预后和免疫治疗效果的新的预测因子。
Background: THUMPD1 is a specific RNA adaptor that assists acetylation of mRNA and production of N4-acetylcytidine (ac4C). However, it remains unclear whether THUMPD1 plays a part in tumorigenesis and therapeutic efficacy. Here, we analyzed the expression profiles and prognostic value of THUMPD1 in pan-cancer and gained insights into the correlation between THUMPD1 expression level and immunotherapy efficacy. Methods: Gene expression pattern and its correlation with prognosis, immune cell infiltration in pan-cancer were obtained from Genotype-Tissue Expression (GTEx), Cancer Cell Line Encyclopedia (CCLE) and The Cancer Genome Atlas (TCGA) databases, with Kaplan–Meier method and Spearman correlation analysis used. Western blotting and immunofluorescence on clinical samples were performed to validate our database-derived results. Correlation between THUMPD1 expression level and immunotherapy responses was also explored, based on clinical cohorts receiving programmed cell death protein 1 ligand (PD-L1) antibody therapy. Finally, gene set enrichment analysis (GSEA) was performed to show the possible tumorigenic mechanism. Results: THUMPD1 was highly expressed in most cancer types, and this elevated expression indicated poor or improved prognosis for different cancers. In kidney renal clear cell carcinoma (KIRC) and rectum adenocarcinoma (READ), patients with higher THUMPD1 expression exhibited a better prognosis, while liver hepatocellular carcinoma (LIHC) patients had worse prognosis. Besides, THUMPD1 was significantly associated with immune cell infiltration, tumor mutational burden (TMB), microsatellite instability (MSI), immune checkpoints and neoantigen in many cancer types. Further, more clinical advantages and therapeutic responses were observed in patients with high THUMPD1 expression. Conclusions: THUMPD1 may serve as a novel predictor to evaluate cancer prognosis and immune therapy efficacy in diverse cancer types.