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Published on: October 9, 2018
DPH2 is a biomarker associated with cell death, immunity and prognosis based on pan-cancer analysis
Maolin Xiao1,2, Shuai Su1,2, Xiangbiao He1,2
1Department of Urology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuanjiagang, Yuzhong District, Chongqing, 400016, China.
Objective:
DPH2, also known as DPH2L2, is one of two human genes similar to yeast dph2. One DPH2 variant has been linked to diphthamide syndrome, a disorder affecting ribosome function. While studies on DPH2 in a single cancer type have been documented, no comprehensive investigations of DPH2 across pan-cancer have been reported, its role in tumor pathogenesis and development remains unclear.
Methods:
The predictive significance and immune and biological roles of DPH2 in 33 different cancer types were investigated. We conducted a comprehensive analysis of DPH2 in pan-cancer using various bioinformatics tools, including expression, prognosis, its association with immune infiltration, cell death, methylation, and many other aspects. In addition, qRT-PCR and immunohistochemistry experiments confirmed DPH2 expression in prostate adenocarcinoma (PRAD) tissues, DPH2 biological function in PRAD was assessed using in vitro experiments, and used immunofluorescence to validate the proteins associated with DPH2.
Results:
The DPH2 expression was high in most tumors and showed significant correlations with OS and PFI. Our experimental findings confirmed that DPH2 is highly expressed in PRAD, while DPH2 knockdown inhibited prostate cancer cell proliferation, invasion, and migration. Furthermore, our data suggest that DPH2 may significantly influence immune cell infiltration. DPH2 was significantly correlated with cell death-related genes. DPH2 can influence cancer progression through changes in DNA methylation levels, or N6-methyladenosine site modification. GSEA and GSVA revealed that DPH2 levels were significantly associated with enrichment for oncogenic and immune-related pathways. Drug sensitivity analysis revealed that the elevated DPH2 expression is linked to development of resistance against numerous anticancer medications.
Conclusion:
DPH2 has potential as a novel prognostic biomarker that may significantly impact tumor onset and progression. Consequently, DPH2 could serve as a target for new cancer treatments.
Insights
DPH2 (diphthamide biosynthesis protein D component 2) is highly expressed in most cancers, promoting tumor growth and immune evasion. This gene may serve as a novel prognostic biomarker and therapeutic target for various cancers.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- DPH2 (diphthamide biosynthesis protein D component 2) is a human gene with limited study in cancer.
- Previous research on DPH2 has been confined to single cancer types, leaving its pan-cancer role unclear.
Purpose of the Study:
- To comprehensively investigate the predictive significance and biological roles of DPH2 across 33 cancer types.
- To explore DPH2's association with tumor pathogenesis, immune infiltration, and therapeutic resistance.
Main Methods:
- Pan-cancer bioinformatics analysis of DPH2 expression, prognosis, immune infiltration, cell death, and methylation.
- Experimental validation of DPH2 expression and function in prostate adenocarcinoma (PRAD) using qRT-PCR, immunohistochemistry, in vitro assays, and immunofluorescence.
Main Results:
- DPH2 is highly expressed in most tumors, correlating with overall survival (OS) and progression-free interval (PFI).
- DPH2 knockdown inhibited PRAD cell proliferation, invasion, and migration, and influenced immune cell infiltration and cell death pathways.
- DPH2 alterations are linked to DNA methylation, N6-methyladenosine modification, oncogenic pathways, and anticancer drug resistance.
Conclusions:
- DPH2 shows potential as a novel prognostic biomarker impacting tumor onset and progression.
- DPH2 represents a potential therapeutic target for developing new cancer treatments.
