胰腺导管腺癌（PDAC）是最恶性的肿瘤之一。内质网应激（ERS）在PDAC的进展中发挥着重要作用。本研究旨在鉴定PDAC中与ERS相关的基因，并建立可靠的风险模型，用于诊断、预后和免疫治疗反应以及探索潜在机制。我们从ArrayExpress、The Cancer Genome Atlas (TCGA)和Genotype-Tissue Expression (GTEx)数据库获得了转录谱和临床数据的PDAC队列。使用单变量Cox回归，LASSO回归和多变量Cox回归分析构建ERS相关的预后签名。应用CIBERSORT和ssGSEA算法探索预后签名与免疫细胞浸润和免疫相关通路之间的相关性。使用GDSC数据库和TIDE算法预测化疗和免疫治疗的反应，识别用于治疗PDAC患者的潜在药物。我们建立和验证了一个包含8个基因（HMOX1，TGFB1，JSRP1，GAPDH，CAV1，CHRNE，CD74和ERN2）的ERS相关的预后签名。高风险评分患者的预后结果较低风险评分患者差。低风险组的PDAC患者可能从免疫治疗中受益。Dasatinib和lapatinib可能在高风险PDAC患者中具有潜在的治疗意义。我们建立和验证了一个包含8个基因的ERS相关的预后签名，可以预测PDAC患者的总体生存结果，与免疫治疗的反应和抗肿瘤药物的敏感性密切相关，并有助于制定临床策略和进行个体化治疗。©2023. 作者。

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors. Endoplasmic reticulum stress (ERS) plays an essential role in PDAC progression. Here, we aim to identify the ERS-related genes in PDAC and build reliable risk models for diagnosis, prognosis and immunotherapy response of PDAC patients as well as investigate the potential mechanism.We obtained PDAC cohorts with transcriptional profiles and clinical data from the ArrayExpress, The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. Univariate Cox regression, LASSO regression and multivariate Cox regression analyses were used to construct an ERS-related prognostic signature. The CIBERSORT and ssGSEA algorithms were applied to explore the correlation between the prognostic signature and immune cell infiltration and immune-related pathways. The GDSC database and TIDE algorithm were used to predict responses to chemotherapy and immunotherapy, identifying potential drugs for treating patients with PDAC.We established and validated an ERS-related prognostic signature comprising eight genes (HMOX1, TGFB1, JSRP1, GAPDH, CAV1, CHRNE, CD74 and ERN2). Patients with higher risk scores displayed worse outcomes than those with lower risk scores. PDAC patients in low-risk groups might benefit from immunotherapy. Dasatinib and lapatinib might have potential therapeutic implications in high-risk PDAC patients.We established and validated an ERS-related prognostic signature comprising eight genes to predict the overall survival outcome of PDAC patients, which closely correlating with the response to immunotherapy and sensitivity to anti-tumor drugs, as well as could be beneficial for formulating clinical strategies and administering individualized treatments.© 2023. The Author(s).