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Updated: Dec 11, 2025
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Comparative Study of Organoids from Patient-Derived Normal and Tumor Colon and Rectal Tissue
Alba Costales-Carrera1,2,3, Asunción Fernández-Barral1,2,3, Pilar Bustamante-Madrid1,2,3
1Departamento de Biología del Cáncer, Instituto de Investigaciones Biomédicas "Alberto Sols", Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid (UAM), 28029 Madrid, Spain.
This study reveals distinct gene expression in rectal tumor organoids compared to normal tissue. Vitamin D (calcitriol) impacts stemness and differentiation genes differently in normal versus tumor organoids.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Colorectal cancer gene expression varies between tumor and normal cells in bulk biopsies.
- Organoid models offer a more precise method to study tumor-specific gene expression.
Purpose of the Study:
- To characterize gene expression profiles of rectal tumor organoids versus normal colon and rectum organoids.
- To investigate the effect of vitamin D on these organoid types.
Main Methods:
- Generation of organoids from endoscopic biopsies of rectal tumors and adjacent normal mucosa.
- RNA-sequencing for gene expression profiling.
- Treatment of organoids with 1α,25-dihydroxyvitamin D3/calcitriol.
Main Results:
- Normal colon and rectum organoids share similar gene expression profiles.
- Rectal tumor organoids exhibit distinct, heterogeneous gene expression, differing from colon tumor organoids.
- Specific genes, including RNA polymerase II subunits (POLR2H, POLR2J), were identified as rectal tumor-specific.
- Calcitriol upregulated stemness genes (LGR5, LRIG1, SMOC2, MSI1) and downregulated differentiation markers (TFF2, MUC2) in normal rectum organoids.
- Rectal tumor organoids showed a different response to calcitriol compared to normal organoids.
Conclusions:
- Rectal tumor organoids provide a better model for studying tumor-specific gene expression than whole tissue biopsies.
- Vitamin D (calcitriol) has differential effects on stemness and differentiation pathways in normal versus rectal tumor organoids.
- Understanding these distinct profiles and responses is crucial for developing targeted therapies for colorectal cancer.
