Lee, Cha Len and O'Kane, Grainne M. and Mason, Warren P. and Zhang, Wen-Jiang and Spiliopoulou, Pavlina and Hansen, Aaron R. and Grant, Robert C. and Knox, Jennifer J. and Stockley, Tracy L. and Zadeh, Gelareh and Chen, Eric X. (2024) Circulating oncometabolite 2-hydroxyglutarate (2HG) as a potential biomarker for isocitrate dehydrogenase (IDH1/2) mutant cholangiocarcinoma. Molecular Cancer Therapeutics, 23 (3). pp. 394-399. ISSN 1535-7163
AI Summary:
Circulating R2HGS2HG ratio (rRS) was significantly increased in IDH-mutant cholangiocarcinoma (CCA) patients compared to wild-type CCA patients. Circulating rRS is a sensitive and specific surrogate biomarker for IDH12 mutations in CCA.AI Topics:
Isocitrate dehydrogenase (IDH) enzymes catalyze the decarboxylation of isocitrate to alpha-ketoglutarate. IDH1/2 mutations preferentially convert αKG to R-2-hydroxyglutarate (R2HG), resulting in R2HG accumulation in tumor tissues. We investigated circulating 2-hydroxyglutate (2HG) as potential biomarkers for patients with IDH-mutant (IDHmt) cholangiocarcinoma (CCA). R2HG and S-2-hydroxyglutarate (S2HG) levels in blood and tumor tissues were analyzed in a discovery cohort of IDHmt glioma and CCA patients. Results were validated in cohorts of CCA and clear cell renal cell carcinoma (ccRCC) patients. The R2HG/S2HG ratio (rRS) was significantly elevated in tumor tissues, but not in blood for IDHmt glioma patients, while circulating rRS was elevated in IDHmt CCA patients. There were overlap distributions of circulating R2HG and total 2HG (t2HG) in both IDHmt and wild-type (IDHwt) CCA patients, while there was minimal overlap in rRS values between IDHmt and IDHwt CCA patients. Using the rRS cut-off value of 1.5, the sensitivity of rRS was 90% and specificity was 96.8%. Circulating rRS is significantly increased in IDHmt CCA patients compare to IDHwt CCA patients. Circulating rRS is a sensitive and specific surrogate biomarker for IDH1/2 mutations in CCA. It can potentially be used as a tool for monitoring IDH-targeted therapy.
Lee, Cha Len
Author
Lee, Cha Len and O'Kane, Grainne M. and Mason, Warren P. and Zhang, Wen-Jiang and Spiliopoulou, Pavlina and Hansen, Aaron R. and Grant, Robert C. and Knox, Jennifer J. and Stockley, Tracy L. and Zadeh, Gelareh and Chen, Eric X. (2024) Circulating oncometabolite 2-hydroxyglutarate (2HG) as a potential biomarker for isocitrate dehydrogenase (IDH1/2) mutant cholangiocarcinoma. Molecular Cancer Therapeutics, 23 (3). pp. 394-399. ISSN 1535-7163
See full publications listO'Kane, Grainne M.
Author
Lee, Cha Len and O'Kane, Grainne M. and Mason, Warren P. and Zhang, Wen-Jiang and Spiliopoulou, Pavlina and Hansen, Aaron R. and Grant, Robert C. and Knox, Jennifer J. and Stockley, Tracy L. and Zadeh, Gelareh and Chen, Eric X. (2024) Circulating oncometabolite 2-hydroxyglutarate (2HG) as a potential biomarker for isocitrate dehydrogenase (IDH1/2) mutant cholangiocarcinoma. Molecular Cancer Therapeutics, 23 (3). pp. 394-399. ISSN 1535-7163
See full publications listMason, Warren P.
Author
Lee, Cha Len and O'Kane, Grainne M. and Mason, Warren P. and Zhang, Wen-Jiang and Spiliopoulou, Pavlina and Hansen, Aaron R. and Grant, Robert C. and Knox, Jennifer J. and Stockley, Tracy L. and Zadeh, Gelareh and Chen, Eric X. (2024) Circulating oncometabolite 2-hydroxyglutarate (2HG) as a potential biomarker for isocitrate dehydrogenase (IDH1/2) mutant cholangiocarcinoma. Molecular Cancer Therapeutics, 23 (3). pp. 394-399. ISSN 1535-7163
See full publications listZhang, Wen-Jiang
Author
Lee, Cha Len and O'Kane, Grainne M. and Mason, Warren P. and Zhang, Wen-Jiang and Spiliopoulou, Pavlina and Hansen, Aaron R. and Grant, Robert C. and Knox, Jennifer J. and Stockley, Tracy L. and Zadeh, Gelareh and Chen, Eric X. (2024) Circulating oncometabolite 2-hydroxyglutarate (2HG) as a potential biomarker for isocitrate dehydrogenase (IDH1/2) mutant cholangiocarcinoma. Molecular Cancer Therapeutics, 23 (3). pp. 394-399. ISSN 1535-7163
See full publications listSpiliopoulou, Pavlina
Author
Cartwright, Douglas and Kidd, Andrew C. and Ansel, Sonam and Ascierto, Maria Libera and Spiliopoulou, Pavlina (2025) Oncogenic signalling pathways in cancer immunotherapy: leader or follower in this delicate dance? International Journal of Molecular Sciences, 26 (9): 4393. ISSN 1661-6596
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Spear, Sarah and Le Saux, Olivia and Mirza, Hasan B. and Iyer, Nayana and Tyson, Katie and Grundland Freile, Fabio and Walton, Josephine B. and Woodman, Chloe and Jarvis, Sheba and Ennis, Darren P. and Aguirre Hernandez, Carmen and Xu, Yuewei and Spiliopoulou, Pavlina and Brenton, James D. and Costa-Pereira, Ana P. and Cook, David P. and Vanderhyden, Barbara C. and Keun, Hector C. and Triantafyllou, Evangelos and Arnold, James N. and McNeish, Iain A. (2024) PTEN loss shapes macrophage dynamics in high grade serous ovarian carcinoma. Cancer Research. ISSN 0008-5472 (In Press)
See full publications listHansen, Aaron R.
Author
Lee, Cha Len and O'Kane, Grainne M. and Mason, Warren P. and Zhang, Wen-Jiang and Spiliopoulou, Pavlina and Hansen, Aaron R. and Grant, Robert C. and Knox, Jennifer J. and Stockley, Tracy L. and Zadeh, Gelareh and Chen, Eric X. (2024) Circulating oncometabolite 2-hydroxyglutarate (2HG) as a potential biomarker for isocitrate dehydrogenase (IDH1/2) mutant cholangiocarcinoma. Molecular Cancer Therapeutics, 23 (3). pp. 394-399. ISSN 1535-7163
Genta, Sofia and Lajkosz, Katherine and Yee, Noelle R. and Spiliopoulou, Pavlina and Heirali, Alya and Hansen, Aaron R. and Siu, Lillian L. and Saibil, Sam and Stayner, Lee-Anne and Yanekina, Maryia and Sauder, Maxwell B. and Keshavarzi, Sareh and Salawu, Abdulazeez and Vornicova, Olga and Butler, Marcus O. and Bedard, Philippe L. and Razak, Albiruni R. Abdul and Rottapel, Robert and Chruscinski, Andrzej and Coburn, Bryan and Spreafico, Anna (2023) Autoimmune PaneLs as PrEdictors of Toxicity in Patients TReated with Immune Checkpoint InhibiTors (ALERT). Journal of Experimental and Clinical Cancer Research, 42 (1): 276. ISSN 1756-9966
See full publications listGrant, Robert C.
Author
Lee, Cha Len and O'Kane, Grainne M. and Mason, Warren P. and Zhang, Wen-Jiang and Spiliopoulou, Pavlina and Hansen, Aaron R. and Grant, Robert C. and Knox, Jennifer J. and Stockley, Tracy L. and Zadeh, Gelareh and Chen, Eric X. (2024) Circulating oncometabolite 2-hydroxyglutarate (2HG) as a potential biomarker for isocitrate dehydrogenase (IDH1/2) mutant cholangiocarcinoma. Molecular Cancer Therapeutics, 23 (3). pp. 394-399. ISSN 1535-7163
See full publications listKnox, Jennifer J.
Author
Lee, Cha Len and O'Kane, Grainne M. and Mason, Warren P. and Zhang, Wen-Jiang and Spiliopoulou, Pavlina and Hansen, Aaron R. and Grant, Robert C. and Knox, Jennifer J. and Stockley, Tracy L. and Zadeh, Gelareh and Chen, Eric X. (2024) Circulating oncometabolite 2-hydroxyglutarate (2HG) as a potential biomarker for isocitrate dehydrogenase (IDH1/2) mutant cholangiocarcinoma. Molecular Cancer Therapeutics, 23 (3). pp. 394-399. ISSN 1535-7163
See full publications listStockley, Tracy L.
Author
Lee, Cha Len and O'Kane, Grainne M. and Mason, Warren P. and Zhang, Wen-Jiang and Spiliopoulou, Pavlina and Hansen, Aaron R. and Grant, Robert C. and Knox, Jennifer J. and Stockley, Tracy L. and Zadeh, Gelareh and Chen, Eric X. (2024) Circulating oncometabolite 2-hydroxyglutarate (2HG) as a potential biomarker for isocitrate dehydrogenase (IDH1/2) mutant cholangiocarcinoma. Molecular Cancer Therapeutics, 23 (3). pp. 394-399. ISSN 1535-7163
See full publications listZadeh, Gelareh
Author
Lee, Cha Len and O'Kane, Grainne M. and Mason, Warren P. and Zhang, Wen-Jiang and Spiliopoulou, Pavlina and Hansen, Aaron R. and Grant, Robert C. and Knox, Jennifer J. and Stockley, Tracy L. and Zadeh, Gelareh and Chen, Eric X. (2024) Circulating oncometabolite 2-hydroxyglutarate (2HG) as a potential biomarker for isocitrate dehydrogenase (IDH1/2) mutant cholangiocarcinoma. Molecular Cancer Therapeutics, 23 (3). pp. 394-399. ISSN 1535-7163
See full publications listChen, Eric X.
Author
Lee, Cha Len and O'Kane, Grainne M. and Mason, Warren P. and Zhang, Wen-Jiang and Spiliopoulou, Pavlina and Hansen, Aaron R. and Grant, Robert C. and Knox, Jennifer J. and Stockley, Tracy L. and Zadeh, Gelareh and Chen, Eric X. (2024) Circulating oncometabolite 2-hydroxyglutarate (2HG) as a potential biomarker for isocitrate dehydrogenase (IDH1/2) mutant cholangiocarcinoma. Molecular Cancer Therapeutics, 23 (3). pp. 394-399. ISSN 1535-7163
See full publications listAvailable under License Creative Commons Attribution Non-commercial No Derivatives.
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