Pancreatic adenocarcinoma (PAAD) is a highly malignant tumor with poor prognosis. However, the relationship between cuproptosis-related genes (CRGs) and its competing endogenous RNA (ceRNA) network with the prognosis of PAAD patients remains unclear. To investigate this relationship, we calculated the difference in CRGs between PAAD tissues and normal tissues using the 'limma' R package. Additionally, we employed least absolute shrinkage and selection operator (LASSO) Cox regression analysis to construct a prognostic signature for CRGs. Survival analysis of patients with PAAD was performed using Kaplan-Meier analysis. Furthermore, we used bioinformatics tools to screen for CRGs-related MicroRNA (miRNA) and lncRNAs. To validate these findings, we conducted real-time quantitative polymerase chain reaction (RT-qPCR), CCK-8, colony formation, and Transwell assays to assess the effect of DLAT in vitro. Our results revealed a cuproptosis-related prognostic signature consisting of 3 prognostic genes (DLAT, LIAS, and LIPT1). Notably, patients with a high-risk score for the CRGs signature exhibited poor prognosis in terms of overall survival (OS) (P < .05). The receiver operating characteristic (ROC) curve was used to evaluate the prognostic signature of CRGs. The results showed that the 1-year, 3-year, and 5-year area under the curve values for predicting OS were 0.62, 0.66, and 0.79, respectively. Additionally, the CRGs-related ceRNA network revealed the regulatory axis of LINC00857/has-miR-1179/DLAT in PAAD. In vitro experiments demonstrated that knockdown of LINC00857 and DLAT inhibited the growth and invasion of PAAD cells. This study identified a CRG-related prognostic signature consisting of 3 biomarkers (DLAT, LIAS, and LIPT1) for PAAD. Furthermore, ceRNA network analysis suggested the involvement of the LINC00857/has-miR-1179/DLAT axis in the development of PAAD. Overall, this study provides theoretical support for the investigation of diagnostic and prognostic biomarkers as well as potential therapeutic targets in PAAD.
