A Cuproptosis-Related Gene Model For Predicting the Prognosis of Clear Cell Renal Cell Carcinoma

Abstract

Despite advances in its treatment, patients diagnosed with clear cell renal cell carcinoma (ccRCC) have a poor prognosis. The mechanism of cuproptosis has been found to differ from other mechanisms that regulate cell death, including apoptosis, iron poisoning, pyrophosphate poisoning, and necrosis. Cuproptosis is an essential component in the regulation of a wide variety of biological processes, such as cell wall remodeling and oxidative stress responses. However, cuproptosis-related genes’ expression in ccRCC patients and their association with the patient’s prognosis remain ambiguous. Evaluation of The Cancer Genome Atlas (TCGA) identified 11 genes associated with cuproptosis that were differently expressed in ccRCC and nearby nontumor tissue. To construct a multigene prognostic model, the prognostic value of 11 genes was assessed and quantified. A signature was constructed by least absolute shrinkage and selection operator (LASSO) Cox regression analysis, and this signature was used to separate ccRCC patients into different risk clusters, with low-risk patients having a much better prognosis. This five-gene signature, when combined with patients’ clinical characteristics, might serve as one independent predictor of overall survival (OS) in ccRCC patients. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that cuproptosis-related genes were enriched in patients with ccRCC. Then, quantitative real-time PCR (qPCR) was employed to verify these genes’ expression. Generally, research has indicated that cuproptosis-related genes are important in tumor immunity and can predict OS of ccRCC patients.

Cuproptosis patterns in papillary renal cell carcinoma are characterized by distinct tumor microenvironment infiltration landscapes

“…Survivability studies showed that patients in the lower-than-normal risk category had a considerably better prognosis. Mei et al (2022) As demonstrated in the scatter graphs, the risk score was positively linked with B cells, M1 Macrophages, and CD4 memory activated T cells. We identified a substantial association between the majority of immune cells and three genes, including APEH and M0 macrophages, CLYBL and M2 macrophages, and ZNF844 and CD4 memory resting T cells.…”

“…Survivability studies showed that patients in the lower-than-normal risk category had a considerably better prognosis. Mei et al (2022) constructed a cuproptosis-related signature that was used to classify clear cell renal cell carcinoma patients into distinct risk clusters, with low-risk patients having a much better prognosis. Because the risk score is inconvenient to apply in practice, we created a nomogram that combines the risk score with clinicopathological variables to estimate patient survival time.…”

Cuproptosis related gene PDHB was identified as a biomarker and its up-regulation inhibited the invasion of renal clear cell carcinoma

“…Numerous past studies have identi ed the importance of cuproptosis-related genes in the ccRCC immune microenvironment and can predict OS in patients with ccRCC [49,50]. Chen's and Zhang's study showed that high expression of FDX1 was associated with a better prognosis of renal clear cell carcinoma and could be used as a potential prognostic indicator and therapeutic target for ccRCC [51,52].…”

Integrated analysis to identify the prognostic and immunotherapeutic roles of coagulation-associated gene signature in clear cell renal cell carcinoma

“…In addition, the risk score distribution, survival status, and expression of CRGs from the signatures are shown in the TCGA training cohort, TCGA validation cohort, and E-MTAB validation cohort (Figures 6E, S2E, S2F). Also, as shown in Figure S3, we compared our signature with previously published signatures in the TCGA dataset, and the results showed that our signature had better predictive performance, especially for 5-year survival (23,24).…”