A1 Refereed original research article in a scientific journal

An immunohistochemistry-based classification of colorectal cancer resembling the consensus molecular subtypes using convolutional neural networks




AuthorsKaprio, Tuomas; Hagström, Jaana; Kasurinen, Jussi; Gkekas, Ioannis; Edin, Sofia; Beilmann-Lehtonen, Ines; Strigard, Karin; Palmqvist, Richard; Gunnarson, Ulf; Böckelman, Camilla; Haglund, Caj

PublisherSpringer Science and Business Media LLC

Publishing placeBERLIN

Publication year2025

JournalScientific Reports

Journal name in sourceScientific Reports

Journal acronymSCI REP-UK

Article number19105

Volume15

Issue1

Number of pages10

ISSN2045-2322

eISSN2045-2322

DOIhttps://doi.org/10.1038/s41598-025-03618-z

Web address https://doi.org/10.1038/s41598-025-03618-z

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/detail/Publication/499008841


Abstract
Colorectal cancer (CRC) represents a major global disease burden with nearly 1 million cancer-related deaths annually. TNM staging has served as the foundation for predicting patient prognosis, despite variation across staging groups. The consensus molecular subtype (CMS) is a transcriptome-based system classifying CRC tumors into four subtypes with different characteristics: CMS1 (immune), CMS2 (canonical), CMS3 (metabolic), and CMS4 (mesenchymal). Transcriptomics is too complex and expensive for clinical implementation; therefore, an immunohistochemical method is needed. The prognostic impact of the immunohistochemistry-based four CMS-like subtypes remains unclear. Due to the complexity and costs associated with transcriptomics, we developed an immunohistochemistry (IHC)-based method supported by convolutional neural networks (CNNs) to define subgroups that resemble CMS biological characteristics. Building on previous IHC-classifiers and incorporating beta-catenin to refine differentiation between CMS2- and CMS3-like profiles, we categorized CRC tumors in a cohort of 538 patients. Classification was successful in 89.4% and 15.9% of tumors were classified as CMS1-like, 35.1% as CMS2-like, 38.7% as CMS3-like, and 11.7% as CMS4-like. CMS2-like patients exhibited the best overall survival (p = 0.018), including when local and metastasized disease were analyzed separately. Our method offers an accessible and clinically feasible CMS-inspired classification, although it does not serve as a replacement for transcriptomic CMS classification.

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Last updated on 2025-12-08 at 15:05