Development and Evaluation of a Novel Cuproptosis‐Related lncRNA Signature for Gastric Cancer Prognosis

Abstract

Background. According to a growing body of research, long noncoding RNAs (lncRNAs) participate in the progress of gastric cancer (GC). Cuproptosis is a distinct kind of programmed cell death, separating it from several other forms of programmed cell death that may be caused by genetic programming. Consequently, it is crucial to examine cuproptosis-related lncRNAs (CRLs) prognostic importance for the prognosis and treatment response in GC. Method. The Cancer Genome Atlas (TCGA) database was used to retrieve RNA-seq data, pertinent clinical information, and somatic mutation data. A list of cuproptosis-related genes (CRGs) was obtained from prior work. We can distinguish prognostic CRLs using coexpression and univariate Cox analysis. Then, using CRLs, we developed a risk prediction model using multivariate Cox regression analysis and the least absolute shrinkage selection operator (LASSO) technique. To evaluate the diagnostic accuracy of this model, a Kaplan-Meier (K-M) survival analysis and a receiver operating characteristic (ROC) analysis were used. Moreover, the relationships between the risk model and immunological function, somatic mutation, and drug sensitivity were also investigated. Results. Using the multivariate Cox analysis technique, we developed a signature based on cuproptosis-related four lncRNAs. We then classified patients into high-risk and low-risk groups based on the likelihood of unfavorable outcomes. The model was subjected to further testing, including K-M survival analysis, ROC analysis, and multivariate Cox regression analysis, all of which proved the model’s exceptional robustness and predictive capacity. In addition, a nomogram that has a strong capacity for prediction ability was built. This nomogram included age, gender, clinical grade, pathologic stage, T stage, and risk score. Furthermore, we discovered substantial disparities in immune function and the number of mutations carried by tumors between the high-risk and low-risk groups. Moreover, this research also found that the IC50 values for 27 chemotherapeutic drugs varied widely across patients within high- and low-risk groups. Conclusion. The proposed 4-CRLs signature is a promising biomarker to predict clinical outcomes in GC.