Background:Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor prognosis, and its progression is driven by epithelial plasticity and tumor microenvironment remodeling. Finding biomarkers that are responsible for the turning point from the early stage to the aggressive phase would facilitate clinical management.Method:In this study, we employed single-cell RNA sequencing to characterize a distinct subpopulation of highly proliferative epithelial cells undergoing a transitional phase during PDAC progression. By linking to cell cycle dysregulation, epithelial differentiation, and clinical staging, we constructed a gene-based risk score model using Lasso Cox regression. The expression of selected genes within the model was further validated using qPCR.Results:The model demonstrated robust predictive power for patient prognosis, TNM staging, and chemotherapy sensitivity. Further analysis of the tumor microenvironment revealed intensified crosstalk between a specific fibroblast subpopulation and transitional epithelial cells, mediated largely by collagen signaling. This stromal–epithelial interaction was found to contribute to the fibrotic barrier characteristic of PDAC. Additionally, immune profiling uncovered altered infiltration patterns, particularly involving natural killer (NK) cells in high-risk patients, suggesting mechanisms of immune tolerance and inhibition.Conclusions:These findings offer potential avenues for early detection, risk stratification, and targeted therapeutic strategies in PDAC.
背景：胰腺导管腺癌（PDAC）是一种侵袭性强、预后不良的恶性肿瘤，其进展受上皮可塑性与肿瘤微环境重塑驱动。寻找能够标志疾病从早期向侵袭阶段转变的关键生物标志物，将有助于临床管理。 方法：本研究采用单细胞RNA测序技术，鉴定出PDAC进展过程中一个处于过渡状态的高增殖上皮细胞亚群。通过关联细胞周期失调、上皮分化状态与临床分期，我们利用Lasso Cox回归构建了基于基因表达的风险评分模型，并通过qPCR对模型中的关键基因进行了表达验证。 结果：该模型在预测患者预后、TNM分期及化疗敏感性方面表现出稳健性能。对肿瘤微环境的深入分析发现，特定成纤维细胞亚群与过渡态上皮细胞间存在以胶原信号为主导的强化交互作用，这种间质-上皮相互作用促进了PDAC特征性纤维化屏障的形成。免疫图谱分析进一步揭示高风险患者存在免疫细胞浸润模式改变，特别是自然杀伤（NK）细胞的功能失调，提示了免疫耐受与抑制的发生机制。 结论：本研究为PDAC的早期检测、风险分层及靶向治疗策略提供了新的潜在途径。
肿瘤(癌症)患者之家