ArticleESMO gastrointestinal oncology2025
Poor-prognosis young-onset colorectal cancer is defined by the mesenchymal subtype and can be predicted by integrating molecular and histopathological characteristics.
Article in ESMO gastrointestinal oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Early-Onset Colorectal Cancer: From Epidemiologic Shift to Life-Course Carcinogenesis and Age-Attuned Care.Current oncology reports · 2026Review
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11 authors.
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Abstract
Background: Young-onset colorectal cancer (CRC), affecting individuals <50 years of age, presents a significant health threat worldwide. The molecular and clinical characteristics of young-onset CRC are poorly understood, complicating the development of effective biomarkers for precision oncology. This study aimed to dissect age-dependent molecular heterogeneity of CRC and establish a model for identifying high-risk young-onset patients. Methods: We analyzed clinical data for 564 439 patient samples across three large cohorts. For molecular characterizations, a subset of 1874 patient samples was used. A deep learning framework was used to analyze hematoxylin-eosin-stained whole-slide images to quantify Shannon diversity indices (SDIs). Subsequently, a multivariate model, integrating SDI, microsatellite status and promoter methylation of miR-200s, was developed for predicting the consensus molecular subtype (CMS)4-mesenchymal subtype, followed by internal and external clinical validations. Results: Young-onset CRC patients exhibited better overall survival but worse relapse-free survival and higher metastasis rates compared with late-onset cases. Molecular subtyping analysis found that young-onset CRC also comprises the same four subtypes (CMS1-4), but the prevalence differs from late-onset CRC. Stratified analysis suggested that the poor outcomes in young-onset CRC were due to higher prevalence of the CMS4-mesenchymal subtype. To predict CMS4, we established an effective risk-scoring model (area under the curve = 0.87) combining molecular and histological markers, with multiple independent validations. Conclusions: CRC shows age-dependent molecular heterogeneity, with young-onset cases more frequently presenting the CMS4 subtype. To predict CMS4, we developed and validated a robust risk-scoring model integrating molecular and histological markers, offering a new translatable tool for more optimized management of young-onset patients.
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