Table2_A Ductal-Cell-Related Risk Model Integrating Single-Cell and Bulk Sequencing Data Predicts the Prognosis of Patients With Pancreatic Adenocarcinoma.XLS

Pancreatic ductal adenocarcinoma (PDAC) is a highly heterogeneous malignancy. Single-cell sequencing (scRNA-seq) technology enables quantitative gene expression measurements that underlie the phenotypic diversity of cells within a tumor. By integrating PDAC scRNA-seq and bulk sequencing data, we aim to extract relevant biological insights into the ductal cell features that lead to different prognoses. Firstly, differentially expressed genes (DEGs) of ductal cells between normal and tumor tissues were identified through scRNA-seq data analysis. The effect of DEGs on PDAC survival was then assessed in the bulk sequencing data. Based on these DEGs (LY6D, EPS8, DDIT4, TNFSF10, RBP4, NPY1R, MYADM, SLC12A2, SPCS3, NBPF15) affecting PDAC survival, a risk score model was developed to classify patients into high-risk and low-risk groups. The results showed that the overall survival was significantly longer in the low-risk group (p < 0.05). The model also revealed reliable predictive power in different subgroups of patients. The high-risk group had a higher tumor mutational burden (TMB) (p < 0.05), with significantly higher mutation frequencies in KRAS and ADAMTS12 (p < 0.05). Meanwhile, the high-risk group had a higher tumor stemness score (p < 0.05). However, there was no significant difference in the immune cell infiltration scores between the two groups. Lastly, drug candidates targeting risk model genes were identified, and seven compounds might act against PDAC through different mechanisms. In conclusion, we have developed a validated survival assessment model, which acted as an independent risk factor for PDAC.

胰腺导管腺癌（pancreatic ductal adenocarcinoma, PDAC）是一种高度异质性的恶性肿瘤。单细胞RNA测序（single-cell RNA sequencing, scRNA-seq）技术可实现定量基因表达检测，该检测是肿瘤内细胞表型多样性的核心支撑。本研究通过整合胰腺导管腺癌的单细胞RNA测序与批量测序数据，旨在挖掘与导管细胞特征相关的生物学机制，这些特征可导致患者预后结局的差异。首先，通过单细胞RNA测序数据分析，我们鉴定出正常组织与肿瘤组织中导管细胞的差异表达基因（differentially expressed genes, DEGs）；随后，利用批量测序数据评估这些差异表达基因对胰腺导管腺癌患者生存的影响。基于这些影响胰腺导管腺癌生存的差异表达基因（LY6D、EPS8、DDIT4、TNFSF10、RBP4、NPY1R、MYADM、SLC12A2、SPCS3、NBPF15），本研究构建了风险评分模型，可将患者划分为高风险组与低风险组。结果显示，低风险组患者的总生存期显著更长（p < 0.05）；该模型在不同患者亚组中均展现出可靠的预测效能。高风险组的肿瘤突变负荷（tumor mutational burden, TMB）更高（p < 0.05），且KRAS与ADAMTS12基因的突变频率显著更高（p < 0.05）；同时，高风险组的肿瘤干细胞评分更高（p < 0.05），但两组患者的免疫细胞浸润评分无显著差异。最后，本研究鉴定出靶向风险模型基因的候选药物，其中7种化合物可通过不同机制发挥抗胰腺导管腺癌作用。综上，本研究构建了经过验证的生存评估模型，该模型可作为胰腺导管腺癌的独立风险因素。