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

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Nic G. Reitsam - , Universität Augsburg, Bayerische Zentrum für Krebsforschung (BZKF), Else Kröner Fresenius Zentrum für Digitale Gesundheit (EKFZ) (Autor:in)
  • Bianca Grosser - , Universität Augsburg, Bayerische Zentrum für Krebsforschung (BZKF) (Autor:in)
  • David F. Steiner - , Google LLC (Autor:in)
  • Veselin Grozdanov - , Universität Ulm (Autor:in)
  • Ellery Wulczyn - , Else Kröner Fresenius Zentrum für Digitale Gesundheit (EKFZ) (Autor:in)
  • Vincenzo L’Imperio - , Università degli Studi di Milano Bicocca (Autor:in)
  • Markus Plass - , Medizinische Universität Graz (Autor:in)
  • Heimo Müller - , Medizinische Universität Graz (Autor:in)
  • Kurt Zatloukal - , Medizinische Universität Graz (Autor:in)
  • Hannah S. Muti - , Klinik und Poliklinik für Viszeral- Thorax- und Gefäßchirurgie, Else Kröner Fresenius Zentrum für Digitale Gesundheit (Autor:in)
  • Jakob N. Kather - , Medizinische Klinik und Poliklinik I, Else Kröner Fresenius Zentrum für Digitale Gesundheit, University of Leeds, Nationales Zentrum für Tumorerkrankungen (NCT) Heidelberg (Autor:in)
  • Bruno Märkl - , Universität Augsburg, Bayerische Zentrum für Krebsforschung (BZKF) (Autor:in)

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

OriginalspracheEnglisch
Aufsatznummer163
Seitenumfang12
FachzeitschriftCommunications medicine
Jahrgang4 (2024)
Ausgabenummer1
PublikationsstatusVeröffentlicht - 15 Aug. 2024
Peer-Review-StatusJa