DLST—a Cuproptosis-related Gene—is a Potential Diagnostic and Prognostic Factor for Clear Cell Renal Cell Carcinoma

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. Not Applicable The details of the IRB/oversight body that provided approval or exemption for the research described are given below: N/A I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the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. Not Applicable 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). Not Applicable I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Not Applicable 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