Consensus molecular subtypes and gene expression in early-onset colorectal cancer

Waddell, O; Sulit, A; Wilson, K; Ramsey, R; Heriot, A; Frizelle, F; Purcell, R

Author(s): Waddell, O; Sulit, A; Wilson, K; Ramsey, R; Heriot, A; Frizelle, F; Purcell, R;
Details: Publication Year 2025-09,Volume 14,Issue #1,Page 2562798
Journal Title: Colorectal Cancer
Publication Type: Research article
Abstract: Background The incidence of early-onset colorectal cancer (EOCRC) is rising in many countries. The drivers of this growing incidence are unclear, and we aimed to determine whether there is a distinct pattern of gene expression in EOCRC compared with late-onset colorectal cancer (LOCRC).; Methods Transcriptomic analysis was carried out on pretreatment tumors from a cohort of 19 EOCRC patients and compared to a control group of 196 LOCRC aged over 65 years. RNA sequencing was used to analyze differential gene expression and gene-set enrichment, as well as assign consensus molecular subtypes (CMS).; Results Thirteen genes were significantly overexpressed in the EOCRC group, including HOXA11, STMN2 and DASH2, and 12 genes overexpressed in the LOCRC group, including ZG16 and MARCO. Gene-set enrichment analysis showed that many of the gene-sets in the EOCRC group were related to cell cycle, while those enriched in the LOCRC group were predominantly related to immune function. When grouping CMS subtypes, LOCRC tended to be immune-rich (CMS1/CMS4), while EOCRC were predominantly CMS2/3.; Conclusion Our results add to the growing literature that EOCRC is a distinct disease from LOCRC. EOCRC have fewer immune-associated gene-sets compared to LOCRC and very low rates of CMS1 and CMS4 subtypes. This may have implications for prognosis and targeted treatments.
Publisher: Taylor & Francis
Department(s): Surgical Oncology; Laboratory Research
Publisher's Version: https://doi.org/10.1080/1758194X.2025.2562798
Open Access at Publisher's Site: https://doi.org/10.1080/1758194X.2025.2562798
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2026-01-16 04:34:23

Last Modified: 2026-01-16 04:35:16