2025/12/01 by Xin Guo, Sai Tian, Xinxing Li +11 · 1 voice
Medicine · #Cancer Cells and Metastasis #Colorectal Cancer Treatments and Studies #Ferroptosis and cancer prognosis
paper · pdf · doi:10.1002/mco2.70492
openalex publication_date 2025/12/01 · openalex created_date 2025/12/09 · openalex updated_date 2026/08/01
Colorectal cancer (CRC) is a complex and heterogeneous disease with limited effective treatment options. To investigate the molecular features and potential therapeutic strategies for CRC patients, including both early-onset colorectal cancer (EOCRC) and late-onset colorectal cancer (LOCRC) cases, a comprehensive multi-omics approach was employed. Whole exome sequencing (WES), RNA sequencing (RNA-seq), and proteomic and phosphoproteomic profiling were performed on paired tumor and normal adjacent tissue (NAT) from 144 CRC patients, totaling 672 samples. Three distinct molecular subtypes were identified, each exhibiting unique clinical prognoses and molecular characteristics. The SI subtype was associated with the worst prognosis and a greater prevalence of EOCRC. Moreover, it exhibited a higher stromal score, characterized by increased infiltration of fibroblasts, mesenchymal stem cells, and adipocytes, when compared with the SII and SIII subtypes. Additionally, the SII subtype showed a higher immune score. Drug testing using cell lines and patient-derived three-dimensional (3D) bioprinted models revealed that SI tumors were more responsive to Alisertib, suggesting subtype-specific therapeutic potential. Our study characterized the multi-omics landscape of CRC, offering critical insights into its molecular heterogeneity. These findings enhance our understanding of the molecular mechanisms underlying CRC and contribute to the development of personalized treatment strategies.