Construction of a Cuproptosis-Related Signature for Predicting Prognosis and Immune Response in Clear Cell Renal Cell Carcinoma

Abstract

Background Cuproptosis is a new form of programmed cell death which induced by copper. The signature of cuproptosis related lncRNAs and mRNAs (CRLM) has not been reported before in clear cell renal cell carcinoma. Methods The RNA-seq, clinical data, and single nucleotide variants (SNV) data of clear cell renal cell carcinoma (ccRCC) were obtained from the Cancer Genome Atlas (TCGA). Cuproptosis related long non-coding RNAs (lncRNAs) were identified via Pearson’s test. Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO) regression analyses were used to further screen prognosis related lncRNAs and mRNAs for signature construction. Cases were then randomly divided into training and testing set groups at ratio 1:1 to validate the cuproptosis signature. Kaplan–Meier survival analysis, receiver operating characteristic (ROC) curve analysis, nomogram, principal components analysis (PCA), gene set enrichment analyses (GSEA), mutation landscape, and therapies response were subsequently conducted with R or perl algorithms. A Japanese ccRCC cohort (n = 98) was used to validate this signature. Results A total of 245 lncRNAs were identified as cuproptosis related. Three of them (AL731577.2, LINC00460, AL133215.2) and cuproptosis related mRNA DBT were finally incorporated into the signature construction. High-risk group patients suffered from lower survival rate. The area under curve (AUC) of the novel signature for 1-, 3-, 5-year survival rates was 0.731, 0.718, 0.745, respectively. The concordance index (C-index) was 0.692. The Japanese cohort showed a good consistence with the results derived from the TCGA dataset. Tumor mutation burden (TMB) was also found to be a risking factor for ccRCC patients. Immune related Gene ontology terms were significantly enriched in high-risk patients. Besides, low-risk patients may be more sensitive to immune check inhibitors (ICIs), Sunitinib, and Pazopanib. High-risk patients may be more sensitive to Sorafenib. Conclusion The cuproptosis related signature is a promising and potential prognostic tool in predicting the survival of patients with ccRCC. It could contribute to precise and individualized ccRCC treatment.