Transcriptomic subtyping of gastrointestinal malignancies

• Published in: Trends in cancer Vol. 10; no. 9; p. 842
• Main Authors: de Back, Tim R, van Hooff, Sander R, Sommeijer, Dirkje W, Vermeulen, Louis
• Format: Journal Article
• Language: English
• Published: United States 01.09.2024
• Subjects: Biomarkers, Tumor - genetics; Gastrointestinal Neoplasms - genetics; Gastrointestinal Neoplasms - pathology; Gene Expression Profiling - methods; Gene Expression Regulation, Neoplastic; Humans; Prognosis; Transcriptome - genetics; Tumor Microenvironment - genetics; colorectal cancer; gastric cancer; transcriptomic subtyping; gastrointestinal malignancies; pancreatic ductal adenocarcinoma; personalized medicine
• ISSN: 2405-8025
• DOI: 10.1016/j.trecan.2024.06.007

Gastrointestinal (GI) cancers are highly heterogeneous at multiple levels. Tumor heterogeneity can be captured by molecular profiling, such as genetic, epigenetic, proteomic, and transcriptomic classification. Transcriptomic subtyping has the advantage of combining genetic and epigenetic information, cancer cell-intrinsic properties, and the tumor microenvironment (TME). Unsupervised transcriptomic subtyping systems of different GI malignancies have gained interest because they reveal shared biological features across cancers and bear prognostic and predictive value. Importantly, transcriptomic subtypes accurately reflect complex phenotypic states varying not only per tumor region, but also throughout disease progression, with consequences for clinical management. Here, we discuss methodologies of transcriptomic subtyping, proposed taxonomies for GI malignancies, and the challenges posed to clinical implementation, highlighting opportunities for future transcriptomic profiling efforts to optimize clinical impact.