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Single-cell transcriptomic landscape deciphers olfactory neuroblastoma subtypes and intra-tumoral heterogeneity

  • Jingyi Yang,
  • Xiaole Song,
  • Huankang Zhang,
  • Quan Liu,
  • Ruoyan Wei,
  • Luo Guo,
  • Cuncun Yuan,
  • Fu Chen,
  • Kai Xue,
  • Yuting Lai,
  • Li Wang,
  • Junfeng Shi,
  • Chengle Zhou,
  • Juan Wang,
  • Yingxuan Yu,
  • Qibing Mei,
  • Li Hu,
  • Huan Wang,
  • Chen Zhang,
  • Qianqian Zhang,
  • Houyong Li,
  • Ye Gu,
  • Weidong Zhao,
  • Huapeng Yu,
  • Jingjing Wang,
  • Zhuofu Liu,
  • Han Li,
  • Shixing Zheng,
  • Juan Liu,
  • Lu Yang,
  • Wanpeng Li,
  • Rui Xu,
  • Jiani Chen,
  • Yumin Zhou,
  • Xiankui Cheng,
  • Yiqun Yu,
  • Dehui Wang,
  • Xicai Sun,
  • Hongmeng Yu

摘要

Olfactory neuroblastoma (ONB) is a rare malignancy known to originate from the olfactory epithelium. The complex tumor ecosystem of this pathology remains unclear. Here, we explored the cellular components within ten ONB tumors and one olfactory mucosa sample based on single-cell RNA profiles. We showed the intra-tumoral heterogeneity by identifying five unique expression programs among malignant epithelial cells. A distinct three-classification system (neural, basal, mesenchymal) for ONB was established according to the distinguished gene expression patterns. Biomarkers for categorizing bulk tumors into uncharacterized subtypes were elucidated. Different responses towards certain chemotherapy regimens could be cautiously inferred according to the molecular features representing the three tumor types, thus helping with precision chemotherapy. We also analyzed subclusters of the tumor microenvironment (TME) and the interactions among different cell types within the TME. The relative abundance of immunosuppressive tumor-associated macrophages suggests potential benefits of immunotherapies targeting macrophages.