Identification and validation of a novel cuproptosis-related lncRNA signature for predicting colorectal cancer patients? survival

Background: Cuproptosis is a novel form of cell death referred to as copper-dependent cytotoxicity. The regulation of proptosis is becoming an increasingly popular cancer treatment modality. To date, few studies have attempted to identify the cuproptosis-related long non-coding RNAs (CRLs). In this study, we sought to investigate the CRLs and construct a novel prognostic model for colorectal cancer (CRC). Methods: The RNA-sequencing data of CRC patients were obtained from The Cancer Genome Atlas database. An analysis was conducted to identify the differentially expressed long non-coding RNAs, and a correlation analysis was performed to identify the CRLs. A univariate Cox analysis was conducted to select the prognostic CRLs. Based on a least absolute shrinkage and selection operator regression analysis, a prognostic signature comprising the 22 identified CRLs was constructed. A survival receiver operating characteristic curve analysis was conducted to evaluate the performance of the signature. Finally, an in vitro analysis was performed to investigate the function of lncRNA AC090116.1 in the CRC cells. Results: A signature comprising 22 CRLs was developed. The patients in the training and validation sets were divided into the low- and high-risk groups and had significantly different survival probabilities. This signature had outstanding prognostic accuracy in predicting the 5-year overall survival of patients [training set, area under the curve (AUC) =0.820; validation set, AUC =0.810]. The pathway enrichment analysis showed that the differential genes between low and high groups were enriched in several important oncogenic- and metastatic-associated processes and pathways. Finally, the in vitro experiments showed that AC090116.1 silencing promoted the cuproptosis processes and suppressed cell proliferation. Conclusions: Our findings provided promising insights into the CRLs involved in CRC. The signature based on CRLs has been successfully devised to prognosticate the clinical outcomes and treatment responses in patients.