Research Paper Volume 15, Issue 21 pp 12314—12329
Cuproptosis-related gene DLAT serves as a prognostic biomarker for immunotherapy in clear cell renal cell carcinoma: multi-database and experimental verification
- 1 Department of Laboratory, Ningbo Urology and Nephrology Hospital, Ningbo, China
- 2 Department of Emergency, Ningbo Urology and Nephrology Hospital, Ningbo, China
- 3 Shanghai Jiao Tong University School of Medicine, Shanghai, China
- 4 Department of Ultrasound, Ningbo Urology and Nephrology Hospital, Ningbo, China
Received: July 16, 2023 Accepted: October 3, 2023 Published: November 7, 2023
https://doi.org/10.18632/aging.205181How to Cite
Copyright: © 2023 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Objective: Renal clear cell carcinoma (ccRCC) is the most common type of renal cancer. Here we aim to explore the prognosis and immunotherapeutic value of copper death-related gene Dihydrolipoamide S-acetyltransferase (DLAT) in ccRCC.
Methods: The mRNA and protein expressions and methylation level of DLAT, as well as the relation of DLAT to survival prognosis, clinical characteristics, biological function, and immune microenvironment and responses in patients with ccRCC were evaluated using multiple databases. In addition, 75 paired ccRCC tissue samples and 3 kinds of cell lines were tested for experimental validation.
Results: Bioinformatics analysis of multiple databases, qRT-PCR, and western blot verified that DLAT expression in ccRCC was lower than that in paracancerous tissues. Patients with low expression of DLAT had a lower survival rate, worse clinical prognosis, stronger immune cell infiltration and expression of immunosuppressive points, and higher tumor immune dysfunction and exclusion (TIDE) scores.
Conclusions: DLAT was identified as an independent prognostic factor in ccRCC and was closely related to the prognosis and immune responses of patients with ccRCC.
Abbreviations
AUC: Area under the curve; BP: Biological processes; CC: Cellular components; CCLE: Cancer Cell Line Encyclopedia; ccRCC: Clear cell renal cell carcinoma; GEO: Gene Expression Omnibus; GO: Gene Ontology; GSEA: Gene Set Enrichment Analysis; GTEx: Genotype-Tissue Expression; ICGC: International Cancer Genome Consortium; ICIs: Immune checkpoint inhibitors; KEGG: Kyoto Encyclopedia of Genes and Genomes; KIRC: Kidney Renal Clear Cell Carcinoma; MF: Molecular functions; MSigDB: Molecular Signatures Database; N: Normal samples; OS: Overall survival; qRT-PCR: Quantitative real-time PCR; RCC: Renal cell carcinoma; RECA: Renal Cell Cancer; ROC: Receiver operating characteristic; T: Tumor samples; TCGA: The Cancer Genome Atlas; TIDE: Tumor Immune Dysfunction and Exclusion; TKIs: Tyrosine kinase inhibitors; TME: Tumor microenvironment.