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Comprehensive Colorectal Cancer Stem Cell Transcriptomic Signatures That Can Predict Patient Prognostic Outcomes
Fumihiko Kakizaki1, Hiroyuki Miyoshi1, Takehito Yamamoto2,3
1Personalized Cancer Therapy Laboratory, Medical Innovation Center, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Cancer Science
|October 31, 2025
Summary
Researchers identified five colorectal cancer stem-like cell (CRC-SC) subtypes based on mRNA expression. One subtype showed favorable outcomes, while others had distinct gene expression patterns influencing prognosis and metastasis in mouse models.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Colorectal cancer (CRC) exhibits significant molecular heterogeneity.
- Colorectal cancer stem-like cells (CRC-SCs) play a crucial role in tumor initiation, progression, and therapeutic resistance.
- Understanding molecular subtypes of CRC-SCs is essential for accurate prognosis and targeted therapy.
Purpose of the Study:
- To identify and characterize distinct molecular subtypes of colorectal cancer stem-like cells (CRC-SCs) based on mRNA expression profiles.
- To correlate these subtypes with patient outcomes and clinical data.
- To develop a practical prognostic indicator for colorectal cancer.
Main Methods:
- Analysis of mRNA expression profiles from 57 patient-derived CRC-SC lines compared to normal colonic epithelial stem-like cells (NCE-SCs).
- Identification of five distinct CRC-SC subtypes based on differential gene expression.
- Validation of subtype-specific gene signatures and a developed prognostic indicator (General Colorectal Cancer Signature - GCS) in independent cohorts and a xenograft mouse model.
Main Results:
- Five CRC-SC subtypes were identified, with one subtype exhibiting significantly increased expression of specific genes (MUC12, PIGR, PLA2G2A, SLC4A4, ZG16) and correlating with favorable patient outcomes.
- The other four subtypes showed high expression of DEFA6, BST2, MAGEA6, or IGF2, respectively, with associated prognostic implications.
- The developed General Colorectal Cancer Signature (GCS) accurately predicted patient outcomes and metastasis development in a mouse model, independent of common driver gene mutations.
Conclusions:
- Distinct molecular subtypes of CRC-SCs exist, characterized by specific gene expression profiles.
- These subtypes and the derived GCS serve as valuable prognostic indicators for colorectal cancer.
- The findings provide a foundation for developing targeted therapeutic strategies and improving outcome prediction in CRC.
