Frontiers in Immunology (Dec 2022)

Delineating the molecular landscape of different histopathological growth patterns in colorectal cancer liver metastases

  • Mingtao Hu,
  • Mingtao Hu,
  • Zhigang Chen,
  • Zhigang Chen,
  • Dandan Hu,
  • Dandan Hu,
  • Shaoyan Xi,
  • Shaoyan Xi,
  • Deshen Wang,
  • Deshen Wang,
  • Xiaolong Zhang,
  • William Pat Fong,
  • William Pat Fong,
  • Lei Wen,
  • Lei Wen,
  • Yanyu Cai,
  • Yanyu Cai,
  • Yunfei Yuan,
  • Yunfei Yuan,
  • Binkui Li,
  • Binkui Li,
  • Xiaojun Wu,
  • Xiaojun Wu,
  • Zhenhai Lu,
  • Zhenhai Lu,
  • Gong Chen,
  • Gong Chen,
  • Liren Li,
  • Liren Li,
  • Peirong Ding,
  • Peirong Ding,
  • Zhizhong Pan,
  • Zhizhong Pan,
  • Desen Wan,
  • Desen Wan,
  • Ziming Du,
  • Ziming Du,
  • Minshan Chen,
  • Minshan Chen,
  • Yuhong Li,
  • Yuhong Li

DOI
https://doi.org/10.3389/fimmu.2022.1045329
Journal volume & issue
Vol. 13

Abstract

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BackgroundHistopathological growth patterns (HGPs) have shown important prognostic values for patients with colorectal cancer liver metastases, but the potential molecular mechanisms remain largely unknown.MethodsWe performed an exploratory analysis by conducting the RNA sequencing of primary colorectal lesions, colorectal liver metastatic lesions and normal liver tissues.FindingsWe found that desmoplastic HGPs of the metastatic lesions were significantly enriched in EMT, angiogenesis, stroma, and immune signaling pathways, while replacement HGPs were enriched in metabolism, cell cycle, and DNA damage repair pathways. With the exception of immune-related genes, the differentially expressed genes of the two HGPs from colorectal liver metastases were mostly inherited from the primary tumor. Moreover, normal liver tissue in the desmoplastic HGP subgroup was markedly enriched in the fibrinous inflammation pathway.ConclusionsWe surmised that HGPs are observable morphological changes resulting from the regulation of molecular expressions, which is the combined effect of the heterogeneity and remodeling of primary tumors seeds and liver soils.

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