Department of Health Statistics, School of Military Preventive Medicine, Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, China.
Shaanxi Provincial Key Laboratory of Infection and Immune Diseases, Shaanxi Provincial People's Hospital, Xi'an, 710068, Shaanxi Province, China.
Hum Genet. 2024 Oct;143(9-10):1109-1129. doi: 10.1007/s00439-024-02663-4. Epub 2024 Mar 25.
Pancreatic ductal adenocarcinoma (PDAC) is a malignant tumor with poor prognosis and high mortality. Although a large number of studies have explored its potential prognostic markers using traditional RNA sequencing (RNA-Seq) data, they have not achieved good prediction effect. In order to explore the possible prognostic signaling pathways leading to the difference in prognosis, we identified differentially expressed genes from one scRNA-seq cohort and four GEO cohorts, respectively. Then Cox and Lasso regression analysis showed that 12 genes were independent prognostic factors for PDAC. AUC and calibration curve analysis showed that the prognostic model had good discrimination and calibration. Compared with the low-risk group, the high-risk group had a higher proportion of gene mutations than the low-risk group. Immune infiltration analysis revealed differences in macrophages and monocytes between the two groups. Prognosis related genes were mainly distributed in fibroblasts, macrophages and type 2 ducts. The results of cell communication analysis showed that there was a strong communication between cancer-associated fibroblasts (CAF) and type 2 ductal cells, and collagen formation was the main interaction pathway.
胰腺导管腺癌（PDAC）是一种预后不良、死亡率高的恶性肿瘤。尽管大量研究已经使用传统 RNA 测序（RNA-Seq）数据探索了其潜在的预后标志物，但并未取得良好的预测效果。为了探索可能导致预后差异的潜在预后信号通路，我们分别从一个 scRNA-seq 队列和四个 GEO 队列中鉴定了差异表达基因。然后 Cox 和 Lasso 回归分析显示，12 个基因是 PDAC 的独立预后因素。AUC 和校准曲线分析表明，该预后模型具有良好的区分度和校准度。与低危组相比，高危组的基因突变比例高于低危组。免疫浸润分析显示两组间巨噬细胞和单核细胞存在差异。预后相关基因主要分布在成纤维细胞、巨噬细胞和 2 型导管中。细胞通讯分析的结果表明，癌相关成纤维细胞（CAF）与 2 型导管细胞之间存在强烈的通讯，胶原形成是主要的相互作用途径。
