Development and Verification of a novel cuproptosis- and immune-associated based prognostic genetic signature for pancreatic ductal adenocarcinoma - 02/03/23
Highlights |
• | Construction of a cuproptosis- and immune-associated prognostic model for PDAC patients. |
• | Cuproptosis might affect the prognosis of PDAC patients via regulating the tumor immune microenvironment. |
• | Cuproptosis might be a promising therapeutic target for PDAC. |
Abstract |
Objective |
Pancreatic ductal adenocarcinoma (PDAC) is a malignancy with a dismal prognosis. Cuproptosis, a novel mechanism mediated by protein lipoylation, results in acute proteotoxic stress and ultimately cell death. However, the clinical impacts of cuproptosis-associated genes and their relationship with immune status in PDAC have not been documented. In this study, we aimed at constructing a cuproptosis- and immune-associated prognostic signature to stratify and predict the prognosis for PDAC patients.
Methods |
The gene expression profiles of 176 PDAC patients from The Cancer Genome Atlas and 167 normal pancreas tissues from the Genotype-Tissue Expression Project were analyzed for differentially expressed genes (DEGs) between PDAC and normal tissues. Pearson correlation analyses were performed to screen out cuproptosis- and immune-associated DEGs. The risk signature of DEGs was constructed using the least absolute shrinkage and selection operator (LASSO) Cox regression analysis, which was validated in the Gene Expression Omnibus (GEO) cohort (n = 114). The immune characteristics in the two risk groups were evaluated using single-sample gene set enrichment analysis and ESTIMATE algorithms.
Results |
A total of 91 cuproptosis- and immune-associated DEGs were screened out, and eight prognostic-related genes were identified using LASSO Cox regression. The prognostic-related genes were then used to construct a risk scoring model, which stratified patients into low- and high-risk groups and were further verified in the external GEO database. The patients in the high-risk group had significantly shorter overall survival than those in the low-risk group. A nomogram based on the risk signature was then constructed. Immune infiltration evaluation suggested that immune status was more activated in the low-risk group. The mutation spectrum also differed between high- and low-risk groups.
Conclusions |
Our cuproptosis- and immune-associated genetic risk signature could be a prognostic biomarker for PDAC. Cuproptosis might be a promising therapeutic target for PDAC.
El texto completo de este artículo está disponible en PDF.Keywords : Pancreatic ductal adenocarcinoma, Cuproptosis, Prognosis, immune
Abbreviations : AUC, DEGs, GEO, GO, GSEA, GTEx, KEGG, LASSO, OS, PDAC, ROC, ssGSEA, TADCs, TCA, TCGA, TNM
Esquema
Vol 47 - N° 3
Artículo 102089- mars 2023 Regresar al número
Artículo precedente
- Sensitivity of fecal immunochemical test and risk factors for interval colorectal cancer in a French population
- Mikaël Canévet, Manon Pruvost-Couvreur, Marie Morvan, Bogdan Badic, Josiane Brousse-Potocki, Tiphaine Kermarrec, Servane Bouzeloc, Jean-Baptiste Nousbaum, Michel Robaszkiewicz, Noémi Reboux, Lucille Quénéhervé
- Prognostic and predictive value of tumoral DNA damage repair protein expression in patients with resected pancreatic cancer
- Furkan Ceylan, Deniz Can Guven, Hakan Taban, Oktay Aktepe, Taha Koray Sahin, Sadettin Kilickap, Alev Turker, Erhan Hamaloglu, Derya Karakoc, Aynur Isik, Aytekin Akyol, Suayib Yalcin, Omer Dizdar
Bienvenido a EM-consulte, la referencia de los profesionales de la salud.
El acceso al texto completo de este artículo requiere una suscripción.
¿Ya suscrito a @@106933@@ revista ?