Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy characterized by a complex tumor microenvironment. Angiogenesis is of paramount importance in the proliferation and metastasis of PDAC. However, currently, there are no well-defined biomarkers available to guide the prognosis and treatment of PDAC. In this study, we investigated the interactions between tumor-associated endothelial cells (TAECs) and tumor cells in PDAC, and identified a specific subset of TAECs characterized by high expression of COL4A1. COL4A1+ endothelial cells interact with tumor cells through the COLLAGEN signaling pathway to promote tumor cell proliferation, migration, and invasion. We also observed activation of HOXD9 in COL4A1+ endothelial cells. Based on these findings, we developed a prognostic model called TaEMS, which accurately predicts patient prognosis. TaEMS identified high-risk patients enriched in cell cycle-related pathways and low-risk patients enriched in focal adhesions, smooth muscle regulation, and immune pathways. Moreover, high-risk patients displayed a reduced level of immune cell infiltration, indicating the presence of a “cold tumor” phenotype. Overall, our study uncovered an intricate crosstalk between TAECs and tumor cells in PDAC, emphasizing the role of HOXD9 and highlighting the potential of TaEMS as a prognostic biomarker for precise therapies.

胰腺导管腺癌（PDAC）是一种高度侵袭性的恶性肿瘤，其特征是复杂的肿瘤微环境。血管生成对于 PDAC 的增殖和转移至关重要。然而，目前尚无明确的生物标志物可用于指导 PDAC 的预后和治疗。在本研究中，我们研究了 PDAC 中肿瘤相关内皮细胞 (TAEC) 与肿瘤细胞之间的相互作用，并鉴定了以 COL4A1 高表达为特征的特定 TAEC 子集。COL4A1+内皮细胞通过COLLAGEN信号通路与肿瘤细胞相互作用，促进肿瘤细胞增殖、迁移和侵袭。我们还观察到 COL4A1+ 内皮细胞中 HOXD9 的激活。基于这些发现，我们开发了一种名为 TaEMS 的预后模型，可以准确预测患者的预后。TaEMS 确定了富含细胞周期相关途径的高风险患者和富含粘着斑、平滑肌调节和免疫途径的低风险患者。此外，高危患者的免疫细胞浸润水平降低，表明存在“冷肿瘤”表型。总体而言，我们的研究发现了 TAEC 和 PDAC 中肿瘤细胞之间复杂的串扰，强调了 HOXD9 的作用，并强调了 TaEMS 作为精确治疗的预后生物标志物的潜力。