Related Experiment Video
Updated: Feb 15, 2026
08:51
Murine Appendectomy Model of Chronic Colitis Associated Colorectal Cancer by Precise Localization of Caecal Patch
Published on: August 24, 2019
10.7K
Elevated d-2-hydroxyglutarate during colitis drives progression to colorectal cancer
Jie Han1, Dakota Jackson1, Janette Holm2
1Division of Gastroenterology, Department of Internal Medicine, Baylor Scott & White Research Institute, Baylor University Medical Center, Dallas, TX 75204.
Summary
Urine d-2-hydroxyglutarate (D2HG) and low tissue d-2-hydroxyglutarate dehydrogenase (D2HGDH) expression indicate higher risk for colon cancer progression in colitis patients. This pathway offers potential therapeutic targets for colitis-associated colon cancer.
Area of Science:
- Biochemistry
- Oncology
- Gastroenterology
Background:
- d-2-hydroxyglutarate (D2HG) is a metabolic byproduct of the tricarboxylic acid cycle.
- d-2-hydroxyglutarate dehydrogenase (D2HGDH) converts D2HG to α-ketoglutarate.
- Altered D2HG metabolism is implicated in cancer development.
Purpose of the Study:
- To investigate the role of the D2HG/D2HGDH pathway in colitis-associated colon cancer (CAC).
- To identify D2HG and D2HGDH as potential biomarkers for CAC progression.
- To explore the D2HG/D2HGDH pathway as a therapeutic target for CAC.
Main Methods:
- Utilized a mouse model of colitis-associated colon cancer.
- Measured urine D2HG levels and colonic D2HGDH expression in mice and ulcerative colitis (UC) patients.
- Investigated the effect of D2HG injection on colitis recovery and tumorigenesis.
- Examined the role of Hypoxia-inducible factor (Hif)-1α in regulating D2HGDH transcription.
Main Results:
- In a mouse CAC model, urine D2HG levels during colitis correlated with polyp counts and dysplasia severity.
- D2HG injection delayed colitis recovery and exacerbated tumorigenesis in mice.
- Colonic D2HGDH expression was decreased at baseline in UC patients who later developed cancer.
- Hif-1α was identified as a key regulator of D2HGDH transcription.
Conclusions:
- Urine D2HG and colonic D2HGDH expression serve as valuable biomarkers for identifying patients at high risk of progressing from colitis to cancer.
- The D2HG/D2HGDH metabolic pathway presents a promising therapeutic target for treating CAC.
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