Converging deep learning and human-observed tumor-adipocyte interaction as a biomarker in colorectal cancer

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Nic G. Reitsam - , Augsburg University, Bavarian Center for Cancer Research (BZKF), Else Kröner-Fresenius Center for Digital Health (EKFZ) (Author)
  • Bianca Grosser - , Augsburg University, Bavarian Center for Cancer Research (BZKF) (Author)
  • David F. Steiner - , Google LLC (Author)
  • Veselin Grozdanov - , Ulm University (Author)
  • Ellery Wulczyn - , Else Kröner-Fresenius Center for Digital Health (EKFZ) (Author)
  • Vincenzo L’Imperio - , University of Milan - Bicocca (Author)
  • Markus Plass - , Medical University of Graz (Author)
  • Heimo Müller - , Medical University of Graz (Author)
  • Kurt Zatloukal - , Medical University of Graz (Author)
  • Hannah S. Muti - , Department of Visceral, Thoracic and Vascular Surgery, Else Kröner Fresenius Center for Digital Health (Author)
  • Jakob N. Kather - , Department of Internal Medicine I, Else Kröner Fresenius Center for Digital Health, University of Leeds, National Center for Tumor Diseases (NCT) Heidelberg (Author)
  • Bruno Märkl - , Augsburg University, Bavarian Center for Cancer Research (BZKF) (Author)

Abstract

Background: Tumor-Adipose-Feature (TAF) as well as SARIFA (Stroma AReactive Invasion Front Areas) are two histologic features/biomarkers linking tumor-associated adipocytes to poor outcomes in colorectal cancer (CRC) patients. Whereas TAF was identified by deep learning (DL) algorithms, SARIFA was established as a human-observed histopathologic biomarker. Methods: To study the overlap between TAF and SARIFA, we performed a systematic pathological review of TAF based on all published image tiles. Additionally, we analyzed the presence/absence of TAF in SARIFA-negative CRC cases to elucidate the biologic and prognostic role of a direct tumor-adipocyte contact. TCGA-CRC gene expression data is investigated to assess the association of FABP4 (fatty-acid binding protein 4) and CD36 (fatty-acid translocase) with both TAF and CRC prognosis. Results: By investigating the TAF/SARIFA overlap, we show that many TAF patches correspond to the recently described SARIFA-phenomenon. Even though there is a pronounced morphological and biological overlap, there are differences in the concepts. The presence of TAF in SARIFA-negative CRCs is not associated with poor outcomes in this cohort, potentially highlighting the importance of a direct tumor-adipocyte interaction. Upregulation of FABP4 and CD36 gene expression seem both linked to a poor prognosis in CRC. Conclusions: By proving the substantial overlap between human-observed SARIFA and DL-based TAF as morphologic biomarkers, we demonstrate that linking DL-based image features to independently developed histopathologic biomarkers is a promising tool in the identification of clinically and biologically meaningful biomarkers. Adipocyte-tumor-cell interactions seem to be crucial in CRC, which should be considered as biomarkers for further investigations.

Details

Original languageEnglish
Article number163
Number of pages12
JournalCommunications medicine
Volume4 (2024)
Issue number1
Publication statusPublished - 15 Aug 2024
Peer-reviewedYes