Construction of a novel signature based on immune-related lncRNA to identify high and low risk pancreatic adenocarcinoma patients

Abstract

BackgroundPancreatic adenocarcinoma is one of the most lethal tumors in the world with a poor prognosis. Thus, an accurate prediction model, which identify patients within high risk of pancreatic adenocarcinoma is needed to adjust the treatment and elevate the prognosis of these patients.MethodsWe obtained RNAseq data of The Cancer Genome Atlas (TCGA) pancreatic adenocarcinoma (PAAD) from UCSC Xena database, identified immune-related lncRNAs (irlncRNAs) by correlation analysis, and identified differential expressed irlncRNAs (DEirlncRNAs) between pancreatic adenocarcinoma tissues from TCGA and normal pancreatic tissues from TCGA and Genotype-Tissue Expression (GTEx). Further univariate and lasso regression analysis were performed to construct prognostic signature model. Then, we calculated the areas under curve and identified the best cut-off value to identify high- and low-risk patients with pancreatic adenocarcinoma. The clinical characteristics, immune cell infiltration, immunosuppressive microenvironment, and chemoresistance were compared between high- and low-risk patients with pancreatic adenocarcinoma.ResultsWe identified 20 DEirlncRNA pairs and grouped the patients by the best cut-off value. We proved that our prognostic signature model possesses a remarkable efficiency to predict prognosis of PAAD patients. The AUC for ROC curve was 0.905 for 1-year prediction, 0.942 for 2-year prediction, and 0.966 for 3-year prediction. Patients in high-risk group have poor survival rate and worse clinical characteristics. We also proved that patients in high-risk groups were in immunosuppressive status and may be resistant to immunotherapy. Anti-cancer drug evaluation was performed based on in-silico predated tool, such as paclitaxel, sorafenib, and erlotinib, may be suitable for PAAD patients in high-risk group.ConclusionsOverall, our study constructed a novel prognostic risk model based on pairing irlncRNAs, exhibited a promising prediction value in patients with pancreatic adenocarcinoma. Our prognostic risk model may help distinguish PAAD patients suitable for medical treatments.