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Published on: December 9, 2016
Pan-cancer analysis identifies RNA helicase DDX1 as a prognostic marker
Baocai Gao1, Xiangnan Li1, Shujie Li2
1State 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.
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.
Insights
The DEAD-box RNA helicase 1 (DDX1) gene shows varied expression across 33 cancers, impacting patient survival and immune responses. DDX1 may serve as a prognostic marker, particularly in renal cancers.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- The DEAD-box RNA helicase (DDX) family is crucial for organismal growth and development.
- DDX1's specific roles in tumorigenesis and various cancers are not fully understood.
- Understanding DDX1's function is key to identifying new cancer biomarkers and therapeutic targets.
Purpose of the Study:
- To investigate the oncogenic roles of DDX1 across a wide range of cancers.
- To analyze DDX1 expression patterns in relation to patient prognosis and survival outcomes.
- To explore the association of DDX1 with tumor microenvironment factors and cellular processes.
Main Methods:
- Utilized The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases for pan-cancer analysis.
- Examined DDX1 expression levels in 33 different tumor types.
- Correlated DDX1 expression with overall survival (OS), disease-free survival (DFS), and immune infiltration.
- Analyzed DDX1 phosphorylation and its impact on cell viability and cancer-related pathways using the CancerSEA database.
Main Results:
- DDX1 expression varies significantly across cancers, being high in breast cancer, cholangiocarcinoma, and colon adenocarcinoma, but low in renal cancers (KIRC, KICH, KIRP).
- Low DDX1 expression in KIRC correlates with better OS and DFS.
- High DDX1 expression is associated with poor OS in adrenocortical carcinoma, bladder urothelial carcinoma, KICH, and liver hepatocellular carcinoma.
- DDX1 expression influences CD8+ T cell infiltration and is linked to microsatellite instability (MSI), tumor mutational burden (TMB), and immune checkpoint blockade therapy (ICT).
- DDX1 depletion affects tumor cell viability and is implicated in DNA repair, RNA transport, and DNA replication pathways.
Conclusions:
- DDX1 exhibits complex, cancer-specific roles in tumorigenesis.
- DDX1 expression levels can serve as a prognostic biomarker for certain cancers, notably renal cancer.
- Further research into DDX1's mechanisms could reveal novel therapeutic strategies for cancer treatment.
