Circulating Oncometabolite 2-hydroxyglutarate as a Potential Biomarker for Isocitrate Dehydrogenase (IDH1/2) Mutant Cholangiocarcinoma
©2023 The Authors; Published by the American Association for Cancer Research..
Isocitrate dehydrogenase (IDH) enzymes catalyze the decarboxylation of isocitrate to alpha-ketoglutarate (αKG). 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 patients with IDHmt glioma and CCA. Results were validated in cohorts of patients with CCA and clear-cell renal cell carcinoma. The R2HG/S2HG ratio (rRS) was significantly elevated in tumor tissues, but not in blood for patients with IDHmt glioma, while circulating rRS was elevated in patients with IDHmt CCA. There were overlap distributions of circulating R2HG and total 2HG in patients with both IDHmt and wild-type (IDHwt) CCA, while there was minimal overlap in rRS values between patients with IDHmt and IDHwt CCA. 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 patients with IDHmt CCA compare with patients with IDHwt CCA. 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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:23 |
|---|---|
| Enthalten in: |
Molecular cancer therapeutics - 23(2024), 3 vom: 04. März, Seite 394-399 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Lee, Cha Len [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
2889-31-8 |
|---|
| Anmerkungen: |
Date Completed 06.03.2024 Date Revised 06.03.2024 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1158/1535-7163.MCT-23-0460 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM365067415 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM365067415 | ||
| 003 | DE-627 | ||
| 005 | 20240306232551.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1158/1535-7163.MCT-23-0460 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1318.xml |
| 035 | |a (DE-627)NLM365067415 | ||
| 035 | |a (NLM)38015561 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Lee, Cha Len |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Circulating Oncometabolite 2-hydroxyglutarate as a Potential Biomarker for Isocitrate Dehydrogenase (IDH1/2) Mutant Cholangiocarcinoma |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 06.03.2024 | ||
| 500 | |a Date Revised 06.03.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a ©2023 The Authors; Published by the American Association for Cancer Research. | ||
| 520 | |a Isocitrate dehydrogenase (IDH) enzymes catalyze the decarboxylation of isocitrate to alpha-ketoglutarate (αKG). 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 patients with IDHmt glioma and CCA. Results were validated in cohorts of patients with CCA and clear-cell renal cell carcinoma. The R2HG/S2HG ratio (rRS) was significantly elevated in tumor tissues, but not in blood for patients with IDHmt glioma, while circulating rRS was elevated in patients with IDHmt CCA. There were overlap distributions of circulating R2HG and total 2HG in patients with both IDHmt and wild-type (IDHwt) CCA, while there was minimal overlap in rRS values between patients with IDHmt and IDHwt CCA. 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 patients with IDHmt CCA compare with patients with IDHwt CCA. 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a alpha-hydroxyglutarate |2 NLM | |
| 650 | 7 | |a 2889-31-8 |2 NLM | |
| 650 | 7 | |a Isocitrate Dehydrogenase |2 NLM | |
| 650 | 7 | |a EC 1.1.1.41 |2 NLM | |
| 650 | 7 | |a Biomarkers |2 NLM | |
| 650 | 7 | |a Ketoglutaric Acids |2 NLM | |
| 650 | 7 | |a IDH1 protein, human |2 NLM | |
| 650 | 7 | |a EC 1.1.1.42. |2 NLM | |
| 650 | 7 | |a Glutarates |2 NLM | |
| 700 | 1 | |a O'Kane, Grainne M |e verfasserin |4 aut | |
| 700 | 1 | |a Mason, Warren P |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Wen-Jiang |e verfasserin |4 aut | |
| 700 | 1 | |a Spiliopoulou, Pavlina |e verfasserin |4 aut | |
| 700 | 1 | |a Hansen, Aaron R |e verfasserin |4 aut | |
| 700 | 1 | |a Grant, Robert C |e verfasserin |4 aut | |
| 700 | 1 | |a Knox, Jennifer J |e verfasserin |4 aut | |
| 700 | 1 | |a Stockley, Tracy L |e verfasserin |4 aut | |
| 700 | 1 | |a Zadeh, Gelareh |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Eric X |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Molecular cancer therapeutics |d 2001 |g 23(2024), 3 vom: 04. März, Seite 394-399 |w (DE-627)NLM122520580 |x 1538-8514 |7 nnns |
| 773 | 1 | 8 | |g volume:23 |g year:2024 |g number:3 |g day:04 |g month:03 |g pages:394-399 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1158/1535-7163.MCT-23-0460 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 23 |j 2024 |e 3 |b 04 |c 03 |h 394-399 | ||