Scholarlink

<p>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 (<i>n</i> = 100) had significantly worse overall survival than those with initial isolated lung-metastatic recurrence (<i>n</i> = 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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 发表日期：

    2025年10月27日

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

摘要

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.