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Background <p>Tissue architecture of cancer deviates from that of normal tissue and is closely linked to various features of cancer, including invasion and tumor immunity. However, pan-cancer analyses of cancer tissue architecture (CTA) remain limited.</p> Methods <p>We applied non-negative matrix factorization to the expression data of 593 CTA-related genes from 28 cancer types in the Cancer Genome Atlas Project dataset, identifying seven distinct CTA signatures.</p> Results <p>A fibrous collagen-related signature, which is related to fibroblasts and the extracellular matrix, was relatively ubiquitous and represents a universal feature of cancer. In contrast, those associated with cell-cell adhesion or cell-stroma adhesion exhibited high tissue specificity. These findings were validated using Pan-Cancer Analysis of Whole Genomes data, spatial transcriptomics, and in vivo and in vitro models. In renal cell carcinoma, we found a strong correlation between network-forming collagen and patient survival, supported by mouse experiments showing that perturbation of this collagen promotes tumor growth. Additionally, several gene mutations and copy number alterations were found to correlate with changes in CTA.</p> Conclusion <p>Our results suggest that CTA can be understood as a combination of components that influence the pathological features of cancer.</p>

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Pan-cancer analysis of RNA expression signatures associated with cancer tissue architecture

  • 期刊论文

  • 发表日期：

    2025年10月17日

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  • Megumi Mogi,
  • Katsushige Kawase,
  • Hiroyoshi Y. Tanaka,
  • Suguru Miyata,
  • Satoko Takemoto,
  • Hideki Ikeda,
  • Eri Katayama,
  • Yuki Nakamura,
  • Ryuta Kojima,
  • Takao Morinaga,
  • Shihori Tanabe,
  • Syuji Yonekura,
  • Mitsunobu R. Kano,
  • Toyoyuki Hanazawa,
  • Masahito Kawazu

摘要

Background

Tissue architecture of cancer deviates from that of normal tissue and is closely linked to various features of cancer, including invasion and tumor immunity. However, pan-cancer analyses of cancer tissue architecture (CTA) remain limited.

Methods

We applied non-negative matrix factorization to the expression data of 593 CTA-related genes from 28 cancer types in the Cancer Genome Atlas Project dataset, identifying seven distinct CTA signatures.

Results

A fibrous collagen-related signature, which is related to fibroblasts and the extracellular matrix, was relatively ubiquitous and represents a universal feature of cancer. In contrast, those associated with cell-cell adhesion or cell-stroma adhesion exhibited high tissue specificity. These findings were validated using Pan-Cancer Analysis of Whole Genomes data, spatial transcriptomics, and in vivo and in vitro models. In renal cell carcinoma, we found a strong correlation between network-forming collagen and patient survival, supported by mouse experiments showing that perturbation of this collagen promotes tumor growth. Additionally, several gene mutations and copy number alterations were found to correlate with changes in CTA.

Conclusion

Our results suggest that CTA can be understood as a combination of components that influence the pathological features of cancer.