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泛癌分析将RNA解旋酶DDX1鉴定为一种预后标志物。

Pan-cancer analysis identifies RNA helicase DDX1 as a prognostic marker.

作者信息

Gao Baocai, Li Xiangnan, Li Shujie, Wang Sen, Wu Jiaxue, Li Jixi

机构信息

State Key Laboratory of Genetic Engineering, School of Life Sciences, MOE Engineering Research Center of Gene Technology, Shanghai Engineering Research Center of Industrial Microorganisms, Fudan University, Shanghai, 200438 China.

Kunming Institute of Physics, Kunming, 650223 China.

出版信息

Phenomics. 2022 Jan 19;2(1):33-49. doi: 10.1007/s43657-021-00034-x. eCollection 2022 Feb.

Abstract

UNLABELLED

The DEAD-box RNA helicase (DDX) family plays a critical role in the growth and development of multiple organisms. is involved in mRNA/rRNA processing and mature, virus replication and transcription, hormone metabolism, tumorigenesis, and tumor development. However, how DDX1 functions in various cancers remains unclear. Here, we explored the potential oncogenic roles of across 33 tumors with The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. is highly expressed in breast cancer (BRCA), cholangiocarcinoma (CHOL), and colon adenocarcinoma (COAD), but it is lowly expressed in renal cancers, including kidney renal clear cell carcinoma (KIRC), kidney chromophobe (KICH), and kidney renal papillary cell carcinoma (KIRP). Low expression of in KIRC is correlated with a good prognosis of overall survival (OS) and disease-free survival (DFS). Highly expressed is linked to a poor prognosis of OS for adrenocortical carcinoma (ACC), bladder urothelial carcinoma (BLCA), KICH, and liver hepatocellular carcinoma (LIHC). Also, the residue Ser481 of DDX1 had an enhanced phosphorylation level in BRCA and ovarian cancer (OV) but decreased in KIRC. Immune infiltration analysis exhibited that expression affected CD8 T cells, and it was significantly associated with MSI (microsatellite instability), TMB (tumor mutational burden), and ICT (immune checkpoint blockade therapy) in tumors. In addition, the depletion of dramatically affected the cell viability of human tumor-derived cell lines. could affect the DNA repair pathway and the RNA transport/DNA replication processes during tumorigenesis by analyzing the CancerSEA database. Thus, our pan-cancer analysis revealed that had complicated impacts on different cancers and might act as a prognostic marker for cancers such as renal cancer.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1007/s43657-021-00034-x.

摘要

未标记

DEAD盒RNA解旋酶(DDX)家族在多种生物体的生长和发育中起关键作用。参与mRNA/rRNA加工与成熟、病毒复制与转录、激素代谢、肿瘤发生及肿瘤发展。然而,DDX1在各种癌症中的作用仍不清楚。在此,我们利用癌症基因组图谱(TCGA)和基因型-组织表达(GTEx)数据库,探索了其在33种肿瘤中的潜在致癌作用。它在乳腺癌(BRCA)、胆管癌(CHOL)和结肠腺癌(COAD)中高表达,但在肾癌中低表达,包括肾透明细胞癌(KIRC)、肾嫌色细胞癌(KICH)和肾乳头状细胞癌(KIRP)。KIRC中低表达与总生存期(OS)和无病生存期(DFS)的良好预后相关。高表达与肾上腺皮质癌(ACC)、膀胱尿路上皮癌(BLCA)、KICH和肝细胞癌(LIHC)的OS不良预后相关。此外,DDX1的丝氨酸481残基在BRCA和卵巢癌(OV)中磷酸化水平增强,但在KIRC中降低。免疫浸润分析显示,其表达影响CD8 T细胞,且与肿瘤中的微卫星不稳定性(MSI)、肿瘤突变负荷(TMB)和免疫检查点阻断治疗(ICT)显著相关。此外,其缺失显著影响人肿瘤来源细胞系的细胞活力。通过分析CancerSEA数据库发现,它在肿瘤发生过程中可能影响DNA修复途径和RNA转运/DNA复制过程。因此,我们的泛癌分析表明,它对不同癌症有复杂影响,可能作为肾癌等癌症的预后标志物。

补充信息

在线版本包含可在10.1007/s43657-021-00034-x获取的补充材料。

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