Identification of a novel cuproptosis-related pattern and its tumor microenvironment infiltration characteristics in pancreatic cancer

Abstract

Purpose Cuproptosis is a novel mechanism of copper-dependent cell death mechanism that can regulate the progression, immune response, and prognosis of tumors. However, the potential roles of cuproptosis-related genes (CRGs) in the clinical outcomes, tumor microenvironment (TME), and immunotherapy of pancreatic cancer (PC) remain unclear. Methods We comprehensively evaluated the CRG patterns in PC samples from two GEO datasets and TCGA based on 19 CRGs. LASSO and multivariate Cox regression were used to construct the cuproptosis model, and a nomogram was constructed to predict the sensitivity of anticancer drugs. Results Methylation regulated the expression level of eight CRGs in PC. Three distinct cuproptosis-related patterns with different biological processes and prognoses were developed. The immune infiltration features of the three cuproptosis patterns were immune-excluded, immune-inflamed, and immune-desert phenotypes, respectively. Higher expression of CRGs indicated a poor prognosis of PC. Based on the cuproptosis phenotype associated signature genes, we constructed a cuproptosis score to study the cuproptosis modification pattern of the individual sample. Univariate and multivariate Cox regression analyses confirmed the cuproptosis risk score model is an independent prognosis biomarker. The high-risk group was characterized by poor prognosis, high expression of CRGs, high frequency of mutation and immune activation, and immunotherapy advantage. The sensitivity of anticancer drugs was significantly different between the high- and low-risk score groups. CRG pattern associated with the clinical-pathological features, TME, and prognosis of PC. Conclusions The newly developed cuproptosis model could guide the design of individualized treatment strategies and facilitate accurate prognosis prediction for PC.