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DDX39 as a predictor of clinical prognosis and immune checkpoint therapy efficacy in patients with clear cell renal cell carcinoma
International Journal of Biological Sciences ( IF 9.2 ) Pub Date : 2021-7-25 , DOI: 10.7150/ijbs.62553
Yewei Bao 1 , Aimin Jiang 1 , Kai Dong 1 , Xinxin Gan 2 , Wenliang Gong 1 , Zhenjie Wu 2 , Bing Liu 2 , Yi Bao 2 , Jie Wang 1, 2 , Linhui Wang 1
Affiliation  

DEAD-box protein 39 (DDX39) has been demonstrated to be a tumorigenic gene in multiple tumor types, but its role in the progression and immune microenvironment of clear cell renal cell cancer (ccRCC) remains unclear. The aim of the present study was to investigate the role of DDX39 in the ccRCC tumor progression, immune microenvironment and efficacy of immune checkpoint therapy./nThe DDX39 expression level was first detected in tumors in the public data and then verified in ccRCC samples from Changzheng Hospital. The prognostic value of DDX39 expression was assessed in the Cancer Genome Atlas (TCGA) and ccRCC patients from Changhai Hospital. The role of DDX39 in promoting ccRCC was analyzed by bioinformatic analysis and in vitro experiments. The association between DDX39 expression and immune cell infiltration and immune inhibitory markers was analyzed, and its value in predicting the immune checkpoint therapy efficacy in ccRCC were evaluated in the public database. DDX39 expression was elevated in Oncomine, GEO and TCGA ccRCC databases, as well as in Changzheng ccRCC samples. In TCGA ccRCC patients, increased DDX39 expression predicted worse overall survival (OS) (p<0.0001) and progression-free interval (PFI) (p<0.0001), and was shown as an independent predictive factor for OS (p=0.002). These findings were consistent with those from Changhai ccRCC patients. In addition, GO and GSEA analysis identified DDX39 as a pro-ccRCC gene. In vitro experiments confirmed the role of DDX39 in promoting ccRCC cell. Finally, DDX39 was found to be positively correlated with a variety of immune inhibitory markers, and could predict the adverse efficacy of immune checkpoint therapy in TIDE analysis. In conclusion, Increased DDX39 in ccRCC patients predicted worse clinical prognosis, promoted ccRCC cell proliferation, migration and invasion, and also predicted adverse efficacy of immune checkpoint therapy.

中文翻译:

DDX39作为透明细胞肾细胞癌患者临床预后和免疫检查点治疗效果的预测因子

DEAD-box 蛋白 39 (DDX39) 已被证明是多种肿瘤类型中的致瘤基因,但其在透明细胞肾细胞癌 (ccRCC) 的进展和免疫微环境中的作用仍不清楚。本研究的目的是探讨 DDX39 在 ccRCC 肿瘤进展、免疫微环境和免疫检查点治疗的疗效中的作用。医院。在长海医院的癌症基因组图谱 (TCGA) 和 ccRCC 患者中评估了 DDX39 表达的预后价值。通过生物信息学分析和体外实验分析了DDX39在促进ccRCC中的作用。分析了 DDX39 表达与免疫细胞浸润和免疫抑制标志物之间的关联,并在公共数据库中评估了其在预测 ccRCC 中免疫检查点治疗疗效方面的价值。DDX39 在 Oncomine、GEO 和 TCGA ccRCC 数据库以及长征 ccRCC 样本中的表达升高。在 TCGA ccRCC 患者中,增加的 DDX39 表达预示着较差的总生存期 (OS) (p <0.0001) 和无进展间期 (PFI) ( p <0.0001),并显示为 OS 的独立预测因素 ( p =0.002)。这些发现与长海ccRCC患者的结果一致。此外,GO 和 GSEA 分析将 DDX39 鉴定为 pro-ccRCC 基因。体外实验证实了 DDX39 在促进 ccRCC 细胞中的作用。最后,发现 DDX39 与多种免疫抑制标志物呈正相关,可在 TIDE 分析中预测免疫检查点疗法的不良反应。总之,ccRCC 患者中 DDX39 升高预示着更差的临床预后,促进 ccRCC 细胞增殖、迁移和侵袭,同时也预示着免疫检查点治疗的不良反应。
更新日期:2021-08-15
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