Pan-cancer analysis of the prognostic and immunological roles of DEAD-box helicase 5 (DDX5) in human tumors

Abstract

Background: Recent studies have demonstrated the significance of the DEAD-box helicase 5 (DDX5) gene, which is involved in pathways concerning the modification of RNA structures. DDX5 functions as a coregulator of cellular transcription and splicing, and participates in the processing of small noncoding RNAs. The aberrant regulation of DDX5 expression possibly plays a significant role in the genesis of cancer. However, there are no comprehensive pan-cancer studies on DDX5. This study is the first to conduct a pan-cancer analysis of DDX5 for aiding the diagnosis and treatment of cancer.Methods: The gene expression, genetic alterations, protein phosphorylation, promoter methylation, immune infiltration, and enrichment analyses of DDX5 were performed using data retrieved from The Cancer Genome Atlas (TCGA), Genotype-tissue Expression (GTEx), Human Protein Atlas (HPA), Tumor Immunological Estimation Resource 2.0 (TIMER2.0), Gene Expression Profiling Interactive Analysis (GEPIA), DNA methylation interactive visualization database (DNMIVD), and Search Tool for the Retrieval of Interaction Genes/Proteins (STRING). Data analyses were performed with the R software and other webtools.Results: The expression of DDX5 mRNA decreased significantly in 17 cancer types, but increased significantly in eight cancer types. The enhanced expression of DDX5 mRNA in the tumor samples was related to decreased overall survival (OS), progression-free interval (PFI), and disease-specific survival (DSS) in three cancers, but increased OS, PFI, and DSS in other cancers. The DNA promoter methylation level was significantly reduced in eight cancer types, and there were exceptions in the methylation levels of the DDX5 promoter in four cancer types. The expression of DDX5 mRNA was highly correlated with the infiltration of CD8+ T cells, cancer-associated fibroblasts, and B cells in a wide variety of malignancies. The findings revealed a strong association between DDX5 and its co-expressed genes in numerous cancer types. Enrichment analysis suggested that DDX5 was associated with multiple cellular pathways, including RNA splicing, Notch signaling pathway, and viral carcinogenesis, which was consistent with the results of previous studies.Conclusion: The findings obtained herein provide further information on the oncogenic potential of DDX5 in diverse tumor types. We propose that DDX5 has important roles in tumor immunity and the diagnosis of cancer.

Role of the DEAD-box RNA helicase DDX5 (p68) in cancer DNA repair, immune suppression, cancer metabolic control, virus infection promotion, and human microbiome (microbiota) negative influence

“…Liu et al performed a comprehensive pan-cancer analysis of the prognostic and immunological roles of DDX5 in human tumors [ 111 ]. The analysis revealed that the DDX5 mRNA increase in tumors is related to decreased overall survival (OS), progression-free interval (PFI), and disease-specific survival (DSS) in 3 cancers but increased OS, PFI, and DSS in others [ 111 ]. While this is important information, it should be recognized that mRNA may not always reflect the protein situation.…”

“…Additionally, studies indicated that degradation of DDX5 (protein) by FL118 induces cancer cell apoptosis but at the same time induces DDX5 mRNA levels [ 46 ]. The other 3 major findings by Liu et al’s analyses include (i) methylation in the DDX5 promoter is significantly reduced in 8 cancer types [ 111 ]; (ii) DDX5 is associated with multiple cellular pathways (e.g., RNA splicing, Notch signaling, and viral carcinogenesis) [ 111 ]; and (iii) DDX5 mRNA expression is highly correlated with the infiltration of CD8( +) T cells, cancer-associated fibroblasts (CAFs), and B cells in a wide variety of malignancies [ 111 ]. The Li et al’s last finding in their pan-cancer analysis of DDX5 mRNA appears to be inconsistent with the potential role of DDX5 (protein) in immune suppression.…”

“…In any case, this is an important area for further investigation. With such up-to-date information for DDX5 [ 111 ], we found that the following publication is extremely intriguing and worthy of detailed review.…”

DDX5 Functions as a Tumor Suppressor in Tongue Cancer

“…DEAD-box polypeptide 5 (DDX5) belongs to the DEAD-box RNA helicase family, the members of which utilize the energy derived from ATP hydrolysis to unwind doublestranded RNA (dsRNA) molecules [4]. DDX5 is a multifunctional protein and participates in numerous cellular processes, including mRNA splicing, mRNA export and translation, and ribosome and miRNA bioDDX5sis [5].…”