DataSheet_1_The immune escape signature predicts the prognosis and immunotherapy sensitivity for pancreatic ductal adenocarcinoma.xlsx

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

背景：胰腺导管腺癌（PDAC）是全球最致命的恶性肿瘤之一。免疫逃逸被认为是导致PDAC免疫治疗失败的原因之一。在本研究中，我们探讨了免疫逃逸相关基因与PDAC患者预后之间的相关性。方法：本研究纳入了来自四个公共数据库（包括癌症基因组图谱（TCGA）、国际癌症基因组联盟（ICGC）、Array-express和基因表达综合数据库（GEO））的1163例PDAC患者。使用Cox回归分析确定了与总生存期（OS）显著相关的182个免疫基因。然后，我们利用多个数据集作为训练队列，建立了免疫逃逸相关基因预后指数（IEGPI）评分，并使用验证队列进行了验证。采用Kaplan-Meier（KM）和Cox回归分析检测IEGPI评分与OS之间的关系。进一步探讨了IEGPI与免疫指数之间的关系。在肿瘤免疫功能障碍和排除（TIDE）数据集中，我们评估了免疫治疗的反应预测值。结果：我们基于与PDAC患者OS预后显著相关的27个免疫逃逸基因建立了IEGPI评分。高IEGPI组的患者与低IEGPI组相比，其总生存率显著降低。在TCGA的32种癌症类型中，通过低IEGPI组和高IEGPI组，可以显著区分出5种癌症类型的生存率。此外，IEGPI评分与多个数据集中的免疫评分呈负相关。在公共数据集中，对接受PD-1和CTLA4治疗的患者，更高的IEGPI与更好的无复发生存期（RFS）和总生存期（OS）相关。