Abstract
Background The prognosis of pancreatic adenocarcinoma (PAAD) is extremely poor and has not been improved. Thus, an effective method to assess the prognosis of patients must be established to improve their survival rate. Method This study investigated immune-related genes that could be used as potential therapeutic targets for PAAD. Level 3 gene expression data from the PAAD cohort and the relevant clinical information were obtained from The Cancer Genome Atlas (TCGA) database. For validation, other PAAD datasets (DSE62452) were downloaded from the Gene Expression Omnibus (GEO) database. The PAAD datasets from TCGA and GEO were used to screen immune-related genes through the Molecular Signatures Database using gene set enrichment analysis. Then, the overlapping immune-related genes of the two datasets were identified. Coexpression networks of the immune-related genes were constructed. Results A signature of three immune-related genes (CKLF, ERAP2, and EREG) was identified in patients with PAAD. The signature could be used to divide the patients with PAAD into high- and low-risk groups based on their median risk score. Multivariate Cox regression analysis was performed to determine the independent prognostic factors of PAAD. Time-dependent receiver operating characteristic (ROC) curve analysis was conducted to assess the prediction accuracy of the prognostic signature. Last, a nomogram was established to assess the individualized prognosis prediction model based on the clinical characteristics and risk score of the TCGA PAAD dataset. The accuracy of the prognostic signature was further evaluated through functional evaluation and principal component analysis. Conclusions The results indicated that the signature of three immune-related genes had excellent predictive value for PAAD. These findings might help improve personalized treatment and medical decisions.
Highlights
BackgroundThe prognosis of pancreatic adenocarcinoma (PAAD) is extremely poor and has not been improved
Pancreatic cancer is a leading cause of death in developed countries, and it is a common malignant tumor worldwide [1]
The pathogenesis of familial pancreatic cancer is closely related to CDKN2A, BRCA1, BRCA2, and PALB2 [9]
Summary
The prognosis of pancreatic adenocarcinoma (PAAD) is extremely poor and has not been improved. An effective method to assess the prognosis of patients must be established to improve their survival rate. Other PAAD datasets (DSE62452) were downloaded from the Gene Expression Omnibus (GEO) database. The. PAAD datasets from TCGA and GEO were used to screen immune-related genes through the Molecular Signatures Database using gene set enrichment analysis. The overlapping immune-related genes of the two datasets were identified. A signature of three immune-related genes (CKLF, ERAP2, and EREG) was identified in patients with PAAD. Time-dependent receiver operating characteristic (ROC) curve analysis was conducted to assess the prediction accuracy of the prognostic signature. A nomogram was established to assess the individualized prognosis prediction model based on the clinical characteristics and risk score of the TCGA PAAD dataset. The accuracy of the prognostic signature was further evaluated through functional evaluation and principal component analysis
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