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

Author

Listed:
  • Xu Guan

    (Chinese Academy of Medical Sciences and Peking Union Medical College
    Chinese Academy of Medical Sciences, Cancer Hospital Affiliated to Shanxi Medical University)

  • Yueyang Zhang

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Ruifang Sun

    (Chinese Academy of Medical Sciences, Cancer Hospital Affiliated to Shanxi Medical University)

  • Guiyu Wang

    (Nangang District)

  • Xiaoman Bi

    (Hainan Medical University)

  • Zhen Zhang

    (Chinese Academy of Medical Sciences, Cancer Hospital Affiliated to Shanxi Medical University)

  • Likun Zan

    (Chinese Academy of Medical Sciences, Cancer Hospital Affiliated to Shanxi Medical University)

  • Yongsheng Meng

    (Chinese Academy of Medical Sciences, Cancer Hospital Affiliated to Shanxi Medical University)

  • Yunxiao Liu

    (Nangang District)

  • Jinyuan Guo

    (Shanxi Medical University)

  • Jian Ma

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Jiale Li

    (Chinese Academy of Medical Sciences, Cancer Hospital Affiliated to Shanxi Medical University)

  • Hanqing Hu

    (Nangang District)

  • Yixun Zhang

    (Chinese Academy of Medical Sciences, Cancer Hospital Affiliated to Shanxi Medical University)

  • Xin Zhang

    (Chinese Academy of Medical Sciences, Cancer Hospital Affiliated to Shanxi Medical University)

  • Maoxi Liu

    (Chinese Academy of Medical Sciences, Cancer Hospital Affiliated to Shanxi Medical University)

  • Bo Jiang

    (Chinese Academy of Medical Sciences, Cancer Hospital Affiliated to Shanxi Medical University)

  • Haiyi Liu

    (Chinese Academy of Medical Sciences, Cancer Hospital Affiliated to Shanxi Medical University)

  • Shuangmei Zou

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Yanfeng Xi

    (Chinese Academy of Medical Sciences, Cancer Hospital Affiliated to Shanxi Medical University)

  • Haitao Zhou

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Wenqi Bai

    (Chinese Academy of Medical Sciences, Cancer Hospital Affiliated to Shanxi Medical University)

  • Deng Wu

    (Hainan Medical University)

  • Xishan Wang

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

Abstract

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.

Suggested Citation

  • 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 & Maox, 2025. "Lymph nodes molecular subtypes unravel lymph nodes heterogeneity and clinical implications in colorectal cancer," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63200-z
    DOI: 10.1038/s41467-025-63200-z
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