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<p>Lymph nodes (LNs) play a pivotal role in colorectal cancer (CRC) progression and immunity, yet their molecular and functional diversity remains poorly understood. By analyzing 630 LNs and 88 primary tumors from 200 CRC patients across four independent cohorts using bulk and single-cell RNA sequencing, we identify four non-metastatic negative LNs (NLN) subtypes (NLN_C1-C4) exhibiting obviously different immune function and stromal expansion. NLN_C3/C4 are characterized by diminished T and B cell activity and fibroblast-driven fibrosis, with follicular dendritic cell loss contributing to B cell dysfunction. Immune checkpoint inhibitors partially reverse these effects, restoring FDC and B cell activity. LNs subtypes demonstrate heterogeneity across patients and within individuals, with higher NLN_C3/C4 proportions associated with advanced tumor stages, poorer survival, and recurrence. Here, we report LNs subtypes as critical manifestations of LN heterogeneity in CRC, providing a basis for improved clinical stratification and LN-targeted therapeutic strategies.</p>

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Lymph nodes molecular subtypes unravel lymph nodes heterogeneity and clinical implications in colorectal cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月22日

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  • Xu Guan,
  • Yueyang Zhang,
  • Ruifang Sun,
  • Guiyu Wang,
  • Xiaoman Bi,
  • Zhen Zhang,
  • Likun Zan,
  • Yongsheng Meng,
  • Yunxiao Liu,
  • Jinyuan Guo,
  • Jian Ma,
  • Jiale Li,
  • Hanqing Hu,
  • Yixun Zhang,
  • Xin Zhang,
  • Maoxi Liu,
  • Bo Jiang,
  • Haiyi Liu,
  • Shuangmei Zou,
  • Yanfeng Xi,
  • Haitao Zhou,
  • Wenqi Bai,
  • Deng Wu,
  • Xishan Wang

摘要

Lymph nodes (LNs) play a pivotal role in colorectal cancer (CRC) progression and immunity, yet their molecular and functional diversity remains poorly understood. By analyzing 630 LNs and 88 primary tumors from 200 CRC patients across four independent cohorts using bulk and single-cell RNA sequencing, we identify four non-metastatic negative LNs (NLN) subtypes (NLN_C1-C4) exhibiting obviously different immune function and stromal expansion. NLN_C3/C4 are characterized by diminished T and B cell activity and fibroblast-driven fibrosis, with follicular dendritic cell loss contributing to B cell dysfunction. Immune checkpoint inhibitors partially reverse these effects, restoring FDC and B cell activity. LNs subtypes demonstrate heterogeneity across patients and within individuals, with higher NLN_C3/C4 proportions associated with advanced tumor stages, poorer survival, and recurrence. Here, we report LNs subtypes as critical manifestations of LN heterogeneity in CRC, providing a basis for improved clinical stratification and LN-targeted therapeutic strategies.