胰腺癌（PAAD）是最致命的恶性肿瘤之一，构成最新一代疫苗技术的信使核糖核酸疫苗有望为胰腺癌的治疗带来新思路。合并并分析癌症基因组图谱-PAAD 和基因型-组织表达数据。使用加权基因共表达网络分析来识别与免疫和氧化应激相关的基因中与肿瘤突变负荷相关的基因模块。通过单变量Cox回归分析筛选差异表达的免疫相关氧化应激基因，并通过非负矩阵分解对这些基因进行分析。经过免疫浸润分析后，采用最小绝对收缩和选择算子回归结合Cox回归构建模型，并根据模型构建后的受试者工作特征曲线和决策曲线分析曲线来预测模型的有效性。最后，利用基因集富集分析结合京都基因和基因组百科全书以及基因本体生物过程分析来分析代谢途径富集。该模型由 ERAP2、间充质上皮转化因子 (MET)、CXCL9 和血管紧张素原 (AGT) 基因组成，可比现有模型更准确地帮助预测胰腺癌患者的预后。 ERAP2 参与免疫激活，在癌症免疫逃避中发挥重要作用。 MET 与肝细胞生长因子结合，导致 c-MET 二聚化和磷酸化。这会激活各种信号通路，包括 MAPK 和 PI3K，以调节癌细胞的增殖、侵袭和迁移。 CXCL9 过表达与患者预后不良相关，并减少 PAAD 肿瘤微环境中 CD8  细胞毒性 T 淋巴细胞的数量。 AGT 被肾素酶裂解产生血管紧张素 1，AGT 转换酶裂解血管紧张素 1 产生血管紧张素 2。胰腺癌诊断后暴露于 AGT 转换酶抑制剂与提高生存率相关。本研究中确定的 4 个基因 - ERAP2、MET、CXCL9 和 AGT - 预计将作为信使核糖核酸疫苗开发的靶标，需要进一步深入研究。版权所有 © 2024 作者。由 Wolters Kluwer Health, Inc. 出版

Adenocarcinoma of the pancreas (PAAD) is one of the deadliest malignant tumors, and messenger ribonucleic acid vaccines, which constitute the latest generation of vaccine technology, are expected to lead to new ideas for the treatment of pancreatic cancer. The Cancer Genome Atlas-PAAD and Genotype-Tissue Expression data were merged and analyzed. Weighted gene coexpression network analysis was used to identify gene modules associated with tumor mutational burden among the genes related to both immunity and oxidative stress. Differentially expressed immune-related oxidative stress genes were screened via univariate Cox regression analysis, and these genes were analyzed via nonnegative matrix factorization. After immune infiltration analysis, least absolute shrinkage and selection operator regression combined with Cox regression was used to construct the model, and the usefulness of the model was predicted based on the receiver operating characteristic curve and decision curve analysis curves after model construction. Finally, metabolic pathway enrichment was analyzed using gene set enrichment analysis combined with Kyoto Encyclopedia of Genes and Genomes and gene ontology biological process analyses. This model consisting of the ERAP2, mesenchymal-epithelial transition factor (MET), CXCL9, and angiotensinogen (AGT) genes can be used to help predict the prognosis of pancreatic cancer patients more accurately than existing models. ERAP2 is involved in immune activation and is important in cancer immune evasion. MET binds to hepatocyte growth factor, leading to the dimerization and phosphorylation of c-MET. This activates various signaling pathways, including MAPK and PI3K, to regulate the proliferation, invasion, and migration of cancer cells. CXCL9 overexpression is associated with a poor patient prognosis and reduces the number of CD8 + cytotoxic T lymphocytes in the PAAD tumor microenvironment. AGT is cleaved by the renin enzyme to produce angiotensin 1, and AGT-converting enzyme cleaves angiotensin 1 to produce angiotensin 2. Exposure to AGT-converting enzyme inhibitors after pancreatic cancer diagnosis is associated with improved survival. The 4 genes identified in the present study - ERAP2, MET, CXCL9, and AGT - are expected to serve as targets for messenger ribonucleic acid vaccine development and need to be further investigated in depth.Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.