DLST—a Cuproptosis-related Gene—is a Potential Diagnostic and Prognostic Factor for Clear Cell Renal Cell Carcinoma
medRxiv (Cold Spring Harbor Laboratory)(2023)
摘要
Clear cell renal cell carcinoma (ccRCC) accounts for the highest number of renal malignancies and 3% of all adult cancers. The incidence of ccRCC is increasing worldwide, and its prognosis is poor. Approximately 30% of the patients are diagnosed at a late stage and are frequently asymptomatic. Cuproptosis is a new type of cell death that is regulated by Cu ions. As cuproptosis is associated with cancer development, we hypothesized that changes in the expression of cuproptosis-related genes (CRGs) are associated with the prognosis of ccRCC, and that CRGs can serve as biomarkers for the diagnosis and prognosis of ccRCC. In the present study, we explored the correlation between CRGs and ccRCC prognosis by analyzing publicly available data. We analyzed the clinical information and RNA-sequencing data in The Cancer Genome Atlas using bioinformatics tools. Dihydrolipoamide S-succinyltransferase ( DLST ) was identified as a novel gene with predictive and diagnostic potential. CRGs were under-expressed in ccRCC samples, and downregulation of DLST was highly associated with poor prognosis. Cox univariate and multivariate regression analyses revealed that DLST could serve as an independent prognostic factor for ccRCC. Further, functional enrichment analysis indicated that low expression of DLST may affect immune function. Our results strongly indicate that DLST plays an important role in ccRCC progression and may serve as an independent diagnostic and prognostic biomarker for ccRCC. Therefore, DLST is a potential therapeutic target for patients with ccRCC.
### Competing Interest Statement
The authors have declared no competing interest.
### Funding Statement
The author(s) received no specific funding for this work.
### Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
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I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.
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I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).
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All RNA sequence profiling files are available from the TCGA database
* AUC
: Areas under the ROC curve
BP
: Biological process
CC
: Cellular component
ccRCC
: Clear cell renal cell carcinoma
CCS
: Copper chaperone for superoxide
CRGs
: Cuproptosis-related genes
DEGs
: Differentially expressed genes
DFS
: Disease-free survival
DLST
: Dihydrolipoamide S-succinyltransferase
FC
: Fold change
GEO
: Gene Expression Omnibus
GO
: Gene Ontology
GSEA
: Gene set enrichment analysis
HR
: Hazard ratio
KEGG
: Kyoto Encyclopedia of Genes and Genomes
MF
: Molecular function
OS
: Overall survival
RCC
: Renal cell carcinoma
ROC
: Receiver operating characteristic
TCA
: Tricarboxylic acid
TCGA
: The Cancer Genome Atlas
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关键词
renal cell,carcinoma,prognostic factor,gene—is,cuproptosis-related
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