Kaprio Tuomas, Hagström Jaana, Kasurinen Jussi, Gkekas Ioannis, Edin Sofia, Beilmann-Lehtonen Ines, Strigård Karin, Palmqvist Richard, Gunnarson Ulf, Böckelman Camilla, Haglund Caj
Department of Surgery, University of Helsinki and Helsinki University Hospital, Haartmaninkatu, 00290, Helsinki, Finland.
Research Programs Unit, Translational Cancer Medicine, University of Helsinki, Helsinki, Finland.
Sci Rep. 2025 May 31;15(1):19105. doi: 10.1038/s41598-025-03618-z.
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 β-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.
结直肠癌(CRC)是一种主要的全球性疾病负担,每年有近100万人死于癌症相关疾病。尽管不同分期组存在差异,但TNM分期一直是预测患者预后的基础。共识分子亚型(CMS)是一种基于转录组的系统,将CRC肿瘤分为四种具有不同特征的亚型:CMS1(免疫型)、CMS2(经典型)、CMS3(代谢型)和CMS4(间充质型)。转录组学对于临床应用来说过于复杂且昂贵;因此,需要一种免疫组织化学方法。基于免疫组织化学的四种CMS样亚型的预后影响仍不清楚。由于与转录组学相关的复杂性和成本,我们开发了一种基于免疫组织化学(IHC)的方法,并由卷积神经网络(CNN)提供支持,以定义类似于CMS生物学特征的亚组。在先前的IHC分类器基础上,并纳入β-连环蛋白以优化CMS2样和CMS3样特征之间的区分,我们对538例患者队列中的CRC肿瘤进行了分类。89.4%的肿瘤分类成功,其中15.