哥伦比亚大学Benjamin Izar小组的一项最新研究发现胰腺导管腺癌患者的细胞状态与转移性器官倾向和生存相关。相关论文于2025年10月27日发表于国际顶尖学术期刊《自然—遗传学》杂志上。

在代表性队列中使用单核RNA测序，研究组发现肝转移复发和肺转移复发的原发性癌细胞的转录谱分别与正常肝脏和肺实质细胞的转录谱相关，这表明在原发部位采用了器官特异性转移程序。这些特征在PDAC肺和肝转移、原发性肺和肝肿瘤以及嗜器官PDAC异种移植模型的转录组中得到证实。这些特征与大型基因组事件无关，大规模肿瘤谱分析数据显示没有预测复发模式的遗传改变。其他分析表明，转移性复发可能在肿瘤发生早期就被确定，并受肿瘤浸润性免疫细胞的影响。因此，原发肿瘤中预先存在的细胞状态似乎会引导器官特异性转移性复发。

据悉，大多数局部胰导管腺癌（PDAC）患者在切除后会复发。对744例PDAC切除患者的分析显示，初始孤立性肝转移复发患者（n=100例）患者的总生存率明显低于初始孤立性肺转移复发患者（n = 31）。

附：英文原文

Title: Cellular states associated with metastatic organotropism and survival in patients with pancreatic ductal adenocarcinoma

Author: Chalabi Hajkarim, Morteza, May, Michael, Amin, Amit Dipak, Jamison, Jacob, Tagore, Somnath, DSouza, Edridge, Caprio, Lindsay, Walsh, Zachary H., Fan, Joy Linyue, Zhang, Mingxuan, Shah, Parin, Abuzaid, Sinan, Michel, Alissa, Dajiang, Sun, Wong, Winston, Shaikh, Neha, Ramaradj, Priyanka, Bakir, Basil, Kluger, Michael D., Chabot, John, Azizi, Elham, Hibshoosh, Hanina, Rustgi, Anil K., Raufi, Alexander G., Manji, Gulam A., Izar, Benjamin

Issue&Volume: 2025-10-27

Abstract: Most patients with localized pancreatic ductal adenocarcinoma (PDAC) experience recurrence after resection. Analysis of 744 patients with resected PDAC revealed that patients with initial isolated liver-metastatic recurrence (n=100) had significantly worse overall survival than those with initial isolated lung-metastatic recurrence (n=31). Using single-nucleus RNA sequencing in a representative cohort, we found that transcriptional profiles of primary cancer cells with liver-metastatic recurrence and lung-metastatic recurrence were correlated with those of normal liver and lung parenchymal cells, respectively, suggesting adoption of organ-specific metastatic programs at the primary site. These signatures were confirmed in transcriptomes of PDAC lung and liver metastases, primary lung and liver tumors, and organotropic PDAC xenograft models. These signatures were independent of large genomic events, and analysis of large-scale tumor profiling data showed no genetic alterations predictive of recurrence patterns. Additional analyses suggested that metastatic recurrence may be determined early in tumorigenesis and influenced by tumor-infiltrating immune cells. Thus, pre-existing cellular states within primary tumors appear to guide organ-specific metastatic relapse.

DOI: 10.1038/s41588-025-02345-5

Source: https://www.nature.com/articles/s41588-025-02345-5