The immune escape signature predicts the prognosis and immunotherapy sensitivity for pancreatic ductal adenocarcinoma

Abstract

BackgroundPancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies worldwide. Immune escape is considered to be a reason for immunotherapy failure in PDAC. In this study, we explored the correlation between immune escape-related genes and the prognosis of PDAC patients.Methods1163 PDAC patients from four public databases, including The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), Array-express, and Gene Expression Omnibus (GEO), were included in our study. Cox regression analysis was used to identify the 182 immune genes which were significantly associated with overall survival (OS). And then we established an immune escape-related gene prognosis index (IEGPI) score using several datasets as the training cohort and validated it using the validation cohort. Kaplan-Meier (KM) and Cox regression analysis were used to detect the relationship of IEGPI score with OS. We further explored the relationship between the IEGPI and immune indexes. And the prediction value of response for immunotherapy in Tumor Immune Dysfunction and Exclusion (TIDE) dataset.ResultsWe establish an IEGPI score based on 27 immune escape genes which were significantly related to the prognosis of OS in PDAC patients. Patients in the high-IEGPI group had a significantly worse overall survival rate compared with that in the low-IEGPI groups by KM curves and cox-regression. 5 of the 32 cancer types in TCGA could be significantly distinguished in survival rates through the low- and high-IEGPI groups. Moreover, the correlation between the IEGPI score was negatively correlated with an immune score in several datasets. And higher IEGPI better recurrence-free survival (RFS) and OS in the patients after patients were treated with both PD-1 and CTLA4 in the public datasets (P<0.05). Intriguingly, by using RT-PCR, we verified that the gene of PTPN2, CEP55, and JAK2 were all higher in the BxPC-3 and PANC-1 than HPDE5 cells. Lastly, we found that the IEGPI score was higher in K-rasLSL.G12D/+, p53LSL.R172H/+, Pdx1Cre (KPC) mice model with anti-PD-L1 than that without anti-PD-L1.ConclusionUsing the immune escape-related genes, our study established and validated an IEGPI score in PDAC patients from the public dataset. IEGPI score has the potential to serve as a prognostic marker and as a tool for selecting tumor patients suitable for immunotherapy in clinical practice.