泛癌症分析发现 RNA 螺旋酶 DDX1 是一种预后标志物。

IF 3.7 Q2 GENETICS & HEREDITY Phenomics (Cham, Switzerland) Pub Date : 2022-01-19 eCollection Date: 2022-02-01 DOI:10.1007/s43657-021-00034-x
Baocai Gao, Xiangnan Li, Shujie Li, Sen Wang, Jiaxue Wu, Jixi Li
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摘要

DEAD-box RNA 螺旋酶(DDX)家族在多种生物的生长和发育过程中发挥着至关重要的作用。DDX1 参与 mRNA/rRNA 处理和成熟、病毒复制和转录、激素代谢、肿瘤发生和肿瘤发展。然而,DDX1 在各种癌症中如何发挥作用仍不清楚。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DDX1在33种肿瘤中的潜在致癌作用。DDX1在乳腺癌(BRCA)、胆管癌(CHOL)和结肠腺癌(COAD)中高表达,但在肾癌(包括肾透明细胞癌(KIRC)、肾嗜色细胞癌(KICH)和肾乳头状细胞癌(KIRP))中低表达。DDX1 在 KIRC 中的低表达与总生存期(OS)和无病生存期(DFS)的良好预后相关。高表达的 DDX1 与肾上腺皮质癌(ACC)、膀胱尿路上皮癌(BLCA)、KICH 和肝肝细胞癌(LIHC)的不良预后有关。此外,DDX1的残基Ser481在BRCA和卵巢癌(OV)中的磷酸化水平升高,但在KIRC中的磷酸化水平降低。免疫浸润分析表明,DDX1的表达会影响CD8+ T细胞,并与肿瘤中的MSI(微卫星不稳定性)、TMB(肿瘤突变负荷)和ICT(免疫检查点阻断疗法)显著相关。此外,DDX1的消耗会极大地影响人类肿瘤衍生细胞系的细胞活力。通过分析 CancerSEA 数据库,DDX1 可能会影响肿瘤发生过程中的 DNA 修复途径和 RNA 转运/DNA 复制过程。因此,我们的泛癌症分析表明,DDX1对不同癌症的影响是复杂的,可能成为肾癌等癌症的预后标志物:在线版本包含补充材料,可查阅 10.1007/s43657-021-00034-x。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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

The DEAD-box RNA helicase (DDX) family plays a critical role in the growth and development of multiple organisms. DDX1 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 DDX1 across 33 tumors with The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. DDX1 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 DDX1 in KIRC is correlated with a good prognosis of overall survival (OS) and disease-free survival (DFS). Highly expressed DDX1 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 DDX1 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 DDX1 dramatically affected the cell viability of human tumor-derived cell lines. DDX1 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 DDX1 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.

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