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Pan-Cancer Analysis of the Cuproptosis-Related Gene DLD
Jiahui Lin1, Guowei Wang2, Sha Cheng1
1Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha 410013, China.
Background:
Cancer affects millions of people each year and imposes a huge economic and social burden worldwide. Cuproptosis is a recently discovered novel mode of cell death. The exact function of the cuproptosis-related gene dihydrolipoamide dehydrogenase (DLD) and its role in pan-cancer is unknown.
Methods:
Data were retrieved from the GTEx, TCGA, and multiple online websites. These data were used to assess the expression, prognosis, and diagnostic value of DLD in various tumors. The relationship of DLD with immune microenvironment immunomodulators, immune checkpoints, tumor mutational load (TMB), microsatellite instability (MSI), and oncology drug sensitivity was explored by correlation analysis.
Results:
The mRNA and protein expression of DLD differs in most cancers. Survival analysis showed that DLD was associated with prognosis with KIRC, KIRP, KICH, and UCS. DLD had a strong diagnostic value in KIRC, GBM, PAAD, and LGG (AUC > 0.9). DLD promoter methylation affects the aberrant expression of LIHC, LUSC, PAAD, READ, and THCA. DLD was negatively correlated with stromal score, immune score, and ESTIMATE score in UCEC, TGCT, LUSC, and SARC. In UCS, resting memory CD4 T cells and activated NK cells were significantly correlated with DLD expression. Significant correlations were also observed between DLD expression and immunomodulators, immune checkpoints, TMB, and MSI in various cancers. Importantly, we also identified a number of potential drugs that may target DLD.
Conclusion:
DLD expression is associated with a variety of tumor prognoses and plays an integral role in tumorigenesis, tumor metabolism, and immunity.
Insights
The dihydrolipoamide dehydrogenase (DLD) gene is linked to various cancer prognoses and plays a role in tumor metabolism and immunity. Its expression and potential as a drug target are explored across multiple cancer types.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genomics
Background:
- Cancer poses a significant global health and economic burden.
- Cuproptosis is a newly identified cell death pathway.
- The role of dihydrolipoamide dehydrogenase (DLD), a cuproptosis-related gene, in pan-cancer remains unclear.
Purpose of the Study:
- To investigate the expression, prognostic, and diagnostic value of DLD in pan-cancer.
- To explore the association of DLD with the tumor immune microenvironment.
- To identify potential therapeutic targets related to DLD.
Main Methods:
- Utilized data from GTEx, TCGA, and online databases.
- Assessed DLD expression, prognosis, and diagnostic utility across various tumors.
- Analyzed correlations between DLD and immune factors, TMB, MSI, and drug sensitivity.
Main Results:
- DLD expression varies significantly across most cancers and is linked to prognosis in KIRC, KIRP, KICH, and UCS.
- DLD demonstrates strong diagnostic value in KIRC, GBM, PAAD, and LGG.
- DLD expression correlates with immune cell infiltration, immunomodulators, immune checkpoints, TMB, and MSI, and potential drug targets were identified.
Conclusions:
- DLD expression is integral to tumorigenesis, tumor metabolism, and immunity.
- DLD is associated with diverse tumor prognoses and presents potential therapeutic avenues.
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