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

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

doi:10.1007/s43657-021-00034-x

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

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

Authors

Baocai Gao¹, Xiangnan Li¹, Shujie Li², Sen Wang¹, Jiaxue Wu¹, Jixi Li¹

Affiliations

¹ 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.
² Kunming Institute of Physics, Kunming, 650223 China.

Abstract

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.

Keywords: DDX1; Pan-cancer analysis; Prognostic marker; RNA helicase; Survival analysis.