Chemical Biopsy for GNMT as Noninvasive and Tumorigenesis-Relevant Diagnosis of Liver Cancer

0568951 - BTÚ 2024 RIV US eng J - Journal Article
Oh, S. - Jo, S. - Kim, H. S. - Mai, V. - Endaya, B. - Neužil, Jiří - Jung, K. H. - Hong, S. - Kim, J. - Park, S.
Chemical Biopsy for GNMT as Noninvasive and Tumorigenesis-Relevant Diagnosis of Liver Cancer.
Analytical Chemistry. Roč. 95, č. 2 (2023), s. 1184-1192. ISSN 0003-2700. E-ISSN 1520-6882
Institutional support: RVO:86652036
Keywords : GLYCINE N-METHYLTRANSFERASE * INFILTRATIVE HEPATOCELLULAR-CARCINOMA * FOLATE-BINDING-PROTEIN
OECD category: Analytical chemistry
Impact factor: 7.4, year: 2022
Method of publishing: Limited access
https://pubs.acs.org/doi/full/10.1021/acs.analchem.2c03944

Early diagnosis of hepatocellular carcinoma (HCC) is difficult, the patients burdened by life-long periodical examinations. Here, a new chemical biopsy approach was developed for noninvasive diagnosis of HCC using urine samples. Bioinformatic screening for tumor suppressors yielded glycine Nmethyltransferase (GNMT) as a biomarker with clinical relevance to HCC tumorigenesis. A liquid chromatography-mass spectrometry (LC-MS)-based chemical biopsy detecting nonradioactive 13C-sarcosine from 13C-glycine was designed to noninvasively assess liver GNMT activity extrahepatically. 13CSarcosine showed a strong correlation with GNMT in normal and cancerous liver cells. In an autochthonous animal model developing visible cancer nodules at 17 weeks, the urinary 13C-sarcosine chemical biopsy exhibited notable changes as early as 8 weeks, showing significant correlations with liver GNMT and molecular pathological changes. Our chemical biopsy approach should facilitate early and noninvasive diagnosis of HCC, with direct relevance to tumorigenesis, which can be straightforwardly applied to other diseases.
Permanent Link: https://hdl.handle.net/11104/0347904