Background: Pancreatic ductal adenocarcinoma (PDAC) has a high incidence of perineural invasion (PNI), a pathological feature of the cancer invasion of nerves. PNI is associated with a poor prognosis, local recurrence and cancer pain. It has been suggested that interactions between nerves and the tumor microenvironment (TME) play a role in PDAC tumorigenesis. Methods: Here, we used Nanostring GeoMx Digital Spatial Profiler to analyze the whole transcriptome of both cancer and nerve cells in the microenvironment of PNI and non-PNI foci from 13 PDAC patients. Conclusions: We identified previously reported pathways involved in PNI, including Axonal Guidance and ROBO-SLIT Signaling. Spatial transcriptomics highlighted the role of PNI foci in influencing the immune landscape of the TME and similarities between PNI and nerve injury response. This study revealed that endocannabinoid and polyamine metabolism may contribute to PNI, cancer growth and cancer pain. Key members of these pathways can be targeted, offering potential novel research avenues for exploring new cancer treatment and/or pain management options in PDAC.
背景：胰腺导管腺癌（PDAC）具有较高的神经周围浸润（PNI）发生率，这是癌症侵犯神经的病理特征。PNI与不良预后、局部复发和癌痛相关。研究表明，神经与肿瘤微环境（TME）之间的相互作用在PDAC肿瘤发生中发挥作用。方法：本研究采用Nanostring GeoMx数字空间分析仪，对13例PDAC患者的PNI及非PNI病灶微环境中的癌细胞和神经细胞进行全转录组分析。结论：我们识别出先前报道的与PNI相关的通路，包括轴突导向通路和ROBO-SLIT信号通路。空间转录组学分析突显了PNI病灶在影响TME免疫景观中的作用，以及PNI与神经损伤反应之间的相似性。本研究揭示，内源性大麻素和多胺代谢可能参与PNI、癌症生长和癌痛过程。这些通路的关键成员可作为潜在治疗靶点，为探索PDAC新型癌症治疗和/或疼痛管理方案提供了新的研究方向。
肿瘤(癌症)患者之家