Background/Objectives: Pancreatic adenocarcinoma (PDAC) remains one of the most lethal cancers, with limited advancements in treatment efficacy due to high rates of chemoresistance. Circulating tumor cells (CTCs) derived from liquid biopsies offer a non-invasive approach to monitoring tumor evolution and identifying molecular mechanisms of resistance. This study aims to longitudinally collect, culture, and characterize CTCs from PDAC patients to elucidate resistance mechanisms and tumor-specific gene expression profiles. Methods: Blood samples from 10 PDAC patients were collected across different treatment stages, yielding 16 CTC cultures. Differential gene expression, pathway dysregulation, and protein–protein interaction studies were utilized, highlighting patient-specific and disease progression-associated changes. Longitudinal comparisons within five patients provided further insights into dynamic molecular changes associated with therapeutic resistance. Results: CTC cultures exhibited the activation of key pathways implicated in PDAC progression and resistance, including TNFα/NF-kB, hedgehog signaling, and the epithelial-to-mesenchymal transition. Longitudinal samples revealed dynamic changes in signaling pathways, highlighting upregulated mechanisms of chemoresistance, including PI3K/Akt/mTOR and TGF-β pathways. Additionally, protein–protein interaction analysis emphasized the role of the immune system in PDAC progression and therapy response. Patient-specific gene expression patterns therefore suggest potential applications for precision medicine. Conclusions: This proof-of-concept study demonstrates the feasibility of longitudinally capturing and analyzing CTCs from PDAC patients. The findings provide critical insights into molecular drivers of chemoresistance and highlight the potential of CTC profiling to inform personalized therapeutic strategies. Future large-scale studies are warranted to validate these findings and further explore CTC-based approaches in PDAC management.
背景/目的：胰腺导管腺癌（PDAC）仍是最致命的恶性肿瘤之一，由于化疗耐药率高，其治疗效果提升有限。基于液体活检的循环肿瘤细胞（CTC）为监测肿瘤演变及识别耐药分子机制提供了非侵入性方法。本研究旨在纵向收集、培养并表征PDAC患者的CTC，以阐明耐药机制及肿瘤特异性基因表达谱。方法：从10名PDAC患者不同治疗阶段采集血液样本，获得16份CTC培养物。通过差异基因表达、通路失调及蛋白质相互作用研究，重点分析患者特异性及疾病进展相关变化。对其中5名患者的纵向比较进一步揭示了与治疗耐药相关的动态分子改变。结果：CTC培养物显示出与PDAC进展及耐药相关的关键通路激活，包括TNFα/NF-kB、Hedgehog信号通路及上皮-间质转化。纵向样本揭示了信号通路的动态变化，凸显了化疗耐药机制的上调，包括PI3K/Akt/mTOR和TGF-β通路。此外，蛋白质相互作用分析强调了免疫系统在PDAC进展及治疗应答中的作用。患者特异性基因表达模式提示了其在精准医疗中的潜在应用价值。结论：本概念验证研究证实了纵向捕获和分析PDAC患者CTC的可行性。研究结果为化疗耐药的分子驱动因素提供了关键见解，并凸显了CTC分析在指导个体化治疗策略方面的潜力。未来需要开展大规模研究以验证这些发现，并进一步探索基于CTC的方法在PDAC治疗中的应用。
肿瘤(癌症)患者之家