Construction and validation of a novel cuproptosis-related long noncoding RNA signature for predicting the outcome of prostate cancer

Abstract

Background: Prostate cancer (PCa) is one of the most common tumors of the urinary system. Cuproptosis is a novel mode of controlled cell death that is related to the development of various tumor types. However, the functions of cuproptosis-related long noncoding RNAs (CRLs) in PCa have not yet been well studied.Methods: In this study, data of PCa patients were obtained from The Cancer Genome Atlas (TCGA) and from the Changhai Hospital. Univariate and multivariate Cox regression analyses and LASSO regression analysis were conducted to screen CRLs linked to the prognosis of PCa patients. A risk score model was constructed on the basis of CRLs to predict prognosis. PCa patients were categorized into high- and low-risk cohorts. The predictive value of the risk score was evaluated by Kaplan–Meier survival analysis, receiver operating characteristic curves, and nomograms. In addition, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to explore possible pathways involving CRLs in PCa. Immune function analysis confirmed the correlation between CRLs and immunity in PCa. Finally, we explored the tumor mutational burden and drug response in the high- and low-risk cohorts.Results: First, we identified seven CRLs (C1orf229, C9orf139, LIPE-AS1, MCPH1-AS1, PRR26, SGMS1-AS1, and SNHG1) that were closely related to prognosis in PCa. The risk score model based on the selected CRLs could accurately predict the prognosis of PCa patients. The high-risk cohort was associated with worse disease-free survival (DFS) time in PCa patients (p < 0.001). ROC curve analysis was performed to confirm the validity of the signature (area under the curve (AUC) at 1 year: 0.703). Nomograms were constructed based on the risk score and clinicopathological features and also exhibited great predictive efficiency for PCa. GO and KEGG analyses showed that the CRLs were mainly enriched in metabolism-related biological pathways in PCa. In addition, immune function analysis showed that patients in the high-risk cohort had higher TMB and were more sensitive to conventional chemotherapy and targeted drugs including doxorubicin, epothilone B, etoposide, and mitomycin C.Conclusion: We constructed a novel CRL-related risk score model to accurately predict the prognosis of PCa patients. Our results indicate that CRLs are potential targets for drug therapy in PCa and provide a possible new direction for personalized treatment of PCa patients.

Identification of novel molecular subtypes and a signature to predict prognosis and therapeutic response based on cuproptosis-related genes in prostate cancer

“…However, in PCa, studies related to cuproptosis are still in the preliminary stage and most of them have focused on cuproptosis-related long non-coding RNA (lncRNA). Several studies have now reported that cuproptosis-related lncRNA have a better prognostic role in predicting PCa ( 43 , 44 ). However, studies on cuproptosis-related coding genes in PCa are rarely reported, and the role of cuproptosis in PCa remains unknown.…”

Comprehensive Analysis of Cuproptosis-related Genes Involved in Prognosis and Tumor Microenvironment Infiltration of Colorectal Cancer

“…Many tumor tissues tend to accumulate high concentrations of copper due to its role in cancer, and copper chelators, including trinitrate and tetrathiomolybdate, have been used in cancer treatment [16]. Cuproptosis, a novel cell death pathway that is different from apoptosis, programmed necrosis, autophagy, and ferroptosis, has recently been identi ed [17] and was reported to participate in the development and progression of multiple cancers [18]. However, the role of cuproptosis in CRC is still unknown.…”

Comprehensive Analysis of Cuproptosis-related Genes in Prognosis and Tumor Microenvironment Infiltration in Colorectal Cancer

“…Recently, cuproptosis, a novel cell death pathway, has been identi ed, which is different from apoptosis, programmed necrosis, autophagy, and ferroptosis [17] . It has been reported that cuproptosis participates in the development and progression of multiple cancers [18] .…”