Cuproptosis-related Gene CEP55 as a Biomarker of Pancreatic Adenocarcinoma via Multi-omics Techniques and Experimental Validation

Abstract

Background. Pancreatic adenocarcinoma (PAAD) is a malignancy with a very poor prognosis. The clinical significance of cuproptosis in PAAD combining single cell data with TCGA data is unclear.

Materials and methods. In this study, we first identified cuproptosis-related genes (CRGs) in PAAD by performing single-cell analysis of the GSE212966 dataset and weighted co-expression network analysis (WCGNA) of the TCGA data. Prognostic models were constructed by using Cox regression and Lasso regression analysis. Finally, survival analysis, immune microenvironment analysis and mutation analysis were carried out.

Results. Based on the cuproptosis-related prognostic model, we divided PAAD patients in the TCGA and GEO cohorts into a high CRGs group and a low CRGs group, with a significant difference in survival time between the two groups (P<0.001). In addition, although the mutation types were similar in the two groups, the high CRGs group had a higher mutation rate of the same mutated genes, which means they were more likely to benefit from immunotherapy.

Conclusions. Finally, CEP55 was identified as the hub gene and in vitro study validated the expression level. Knock-down of the CEP55 could inhibit the cell proliferation and invasion of PAAD. This study may provide a new approach to the diagnosis and treatment of PAAD.