Delineating the early dissemination mechanisms of acral melanoma by integrating single-cell and spatial transcriptomic analyses

  • Nat Commun. 2023 Dec 8;14(1):8119. doi: 10.1038/s41467-023-43980-y.
Chuanyuan Wei  #  1  2 ,  Wei Sun  #  3  4 ,  Kangjie Shen  #  1  2 ,  Jingqin Zhong  3  4 ,  Wanlin Liu  3  4 ,  Zixu Gao  1  2 ,  Yu Xu  3  4 ,  Lu Wang  1  2 ,  Tu Hu  3  4 ,  Ming Ren  1  2 ,  Yinlam Li  1  2 ,  Yu Zhu  1  2 ,  Shaoluan Zheng  5 ,  Ming Zhu  1  2 ,  Rongkui Luo  6 ,  Yanwen Yang  1  2 ,  Yingyong Hou  6 ,  Fazhi Qi  1  2 ,  Yuhong Zhou  7 ,  Yong Chen  8  9 ,  Jianying Gu  10  11  12
Affiliations
  • 1. Department of Plastic and Reconstructive Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, P. R. China.
  • 2. Cancer center, Zhongshan Hospital, Fudan University, Shanghai, 200032, P. R. China.
  • 3. Department of Musculoskeletal Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, P. R. China.
  • 4. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, P. R. China.
  • 5. Department of Plastic and Reconstructive Surgery, Xiamen Branch of Zhongshan Hospital, Fudan University, Xiamen, 361015, P. R. China.
  • 6. Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, P. R. China.
  • 7. Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, 200032, P. R. China. [email protected].
  • 8. Department of Musculoskeletal Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, P. R. China. [email protected].
  • 9. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, P. R. China. [email protected].
  • 10. Department of Plastic and Reconstructive Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, P. R. China. [email protected].
  • 11. Cancer center, Zhongshan Hospital, Fudan University, Shanghai, 200032, P. R. China. [email protected].
  • 12. Department of Plastic and Reconstructive Surgery, Xiamen Branch of Zhongshan Hospital, Fudan University, Xiamen, 361015, P. R. China. [email protected].
  • # Contributed equally.
PMID: 38065972 DOI: 10.1038/s41467-023-43980-y
Abstract

Acral melanoma (AM) is a rare subtype of melanoma characterized by a high incidence of lymph node (LN) metastasis, a critical factor in tumor dissemination and therapeutic decision-making. Here, we employ single-cell and spatial transcriptomic analyses to investigate the dynamic evolution of early AM dissemination. Our findings reveal substantial inter- and intra-tumor heterogeneity in AM, alongside a highly immunosuppressive tumor microenvironment and complex intercellular communication networks, particularly in patients with LN metastasis. Notably, we identify a strong association between MYC+ Melanoma (MYC+MEL) and FGFBP2+NKT cells with LN metastasis. Furthermore, we demonstrate that LN metastasis requires a metabolic shift towards fatty acid oxidation (FAO) induced by MITF in MYC+MEL cells. Etomoxir, a clinically approved FAO inhibitor, can effectively suppress MITF-mediated LN metastasis. This comprehensive dataset enhances our understanding of LN metastasis in AM, and provides insights into the potential therapeutic targeting for the management of early AM dissemination.

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