An in-house MS2 database (BiotreeDB) was applied in metabolite annotation. The cutoff for annotation was set at 0.3.
"],"repository":["MetaboLights"],"study_status":["Public"],"ptm_modification":[""],"instrument_platform":["Liquid Chromatography MS - positive - hilic","Liquid Chromatography MS - negative - hilic"],"chromatography_protocol":["The quality control (QC) sample was prepared by mixing an equal aliquot of the supernatants from all of the samples. LC-MS/MS analyses were performed using an UHPLC system (Vanquish, Thermo Fisher Scientific) with a Waters BEH Amide column (2.1 mm × 50 mm, 1.7 μm) coupled to Orbitrap Exploris 120 mass spectrometer (Orbitrap MS, Thermo). The mobile phase consisted of 25 mmol/L ammonium acetate and 25 mmol/L ammonia hydroxide in water(pH = 9.75)(A) and acetonitrile (B). The auto-sampler temperature was 4°C, and the injection volume was 2 μL.
"],"publication":["Methionine intervention induces PD-L1 expression to enhance the immune checkpoint therapy response in MTAP-deleted osteosarcoma. 10.1016/j.xcrm.2025.101977. PMID:39983717"],"submitter_name":["HAORAN MU"],"submitter_affiliation":["Shanghai Jiao Tong University"],"organism_part":["feces"],"technology_type":["mass spectrometry assay"],"disease":[""],"extraction_protocol":["500 μL extract solution (methanol: acetonitrile: water = 2: 2: 1, with isotopically-labelled internal standard mixture) was added. Then the samples were homogenized at 35 Hz for 4 min and sonicated for 5 min in ice-water bath. The homogenization and sonication cycle were repeated for 3 times. Then the samples were incubated for 1 h at −40°C and centrifuged at 12000 rpm (RCF = 13800(×g), R = 8.6cm) for 15 min at 4°C. The resulting supernatant was transferred to a fresh glass vial for analysis.
"],"organism":["Mus musculus"],"full_dataset_link":["https://www.ebi.ac.uk/metabolights/MTBLS11985"],"author":["Wei Sun. Shanghai First People's Hospital. Haining Road 85, Hongkou, Shanghai, China. viv-sun@sjtu.edu.cn.","Yining Tao. Shanghai First People's Hospital. Wujin Road 85, Hongkou, Shanghai, China. tyn923klaus@163.com.","Haoran Mu. Shanghai First People's Hospital. Wujin Road 85, Hongkou, Shanghai, China. dr_muhaoran@163.com.","Qi Zhang. Shanghai Jiao Tong University. Wujin Road 85, Hongkou, Shanghai, China. 13783461257@163.com."],"data_transformation_protocol":["The raw data were converted to the mzXML format using ProteoWizard and processed with an in-house program, which was developed using R and based on XCMS, for peak detection, extraction, alignment, and integration.
"],"study_factor":["MTAP deleted osteosarcoma dunn MTAP-/ in methionine restriction diet","Biological replicate"],"submitter_email":["dr_muhaoran@163.com"],"sample_collection_protocol":["25 mg of sample was weighted to an EP tube.
"],"omics_type":["Metabolomics"],"study_design":["Metabolomics","MTAP","Mus musculus","untargeted analysis","Thermo Scientific Vanquish Flex UHPLC System","Thermo Scientific Orbitrap Exploris 120","bone cancer","experimental blank","feces","osteosarcoma","experimental sample"],"curator_keywords":["Metabolomics","MTAP","Mus musculus","untargeted analysis","Thermo Scientific Vanquish Flex UHPLC System","Thermo Scientific Orbitrap Exploris 120","bone cancer","experimental blank","feces","osteosarcoma","experimental sample"],"mass_spectrometry_protocol":["The Orbitrap Exploris 120 mass spectrometer was used for its ability to acquire MS/MS spectra on information-dependent acquisition (IDA) mode in the control of the acquisition software (Xcalibur, Thermo). In this mode, the acquisition software continuously evaluates the full scan MS spectrum. The ESI source conditions were set as following: sheath gas flow rate as 50 Arb, Aux gas flow rate as 15 Arb, capillary temperature 320°C, full MS resolution as 60000, MS/MS resolution as 30000 collision energy as 20/30/40 in NCE mode, spray Voltage as 3 kV (positive) or −3 kV (negative), respectively.
"],"metabolite_name":["Taurine","D-Fructose","Allantoin","Acetovanillone","Mahanimbine","Alantolactone","Aspartame","D-Xylose","Deoxyinosine","L-Threonine","2-Hydroxyethanesulfonate","N-Acetylvaline","L-Erythrulose","2-Methylbenzoic acid","L-Leucine","Prostaglandin H2","alpha-Ketoisovaleric acid","Oxoglutaric acid","N-Acetyl-D-glucosamine","Phenylpyruvic?acid","Hepoxilin A3","D-Glucuronic acid","3-Hydroxyanthranilic acid","L-Sorbose","Pyruvic acid","Pyrrole-2-carboxylic acid","1,2,3-Trihydroxybenzene","12-Ketodeoxycholic acid","D-Glutamine","cis,cis-Muconic acid","Gentisic acid","Glycolic acid","Glutaric acid","13S-hydroxyoctadecadienoic acid","Pentadecanoic acid","N-Acetylglutamic acid","Deoxyuridine","N-Acetyl-beta-alanine","4-Hydroxybenzeneacetonitrile","3'-Sialyllactose","Gentisaldehyde","3-(2-Hydroxyphenyl)propanoic acid","2-Ethyl-2-Hydroxybutyric acid","N-Acetyl-5-hydroxytryptamine","Uracil","N-Acetylneuraminic acid","2-Oxo-4-methylthiobutanoic acid","Mycophenolic acid","Glyceraldehyde","Sinapic acid","Maltotetraose","beta-Hydroxypyruvic acid","11Z-Eicosenoic acid","Xanthurenic acid","16-Hydroxy hexadecanoic acid","4-Dodecylbenzenesulfonic Acid","IDP","Oxobutanedioic acid","Vanillic acid","Cholesterol sulfate","Glyceric acid","Benzyl acetate","Gallic acid","3-Furoic acid","Homoveratric acid","Alpha-Hydroxyisobutyric acid","L-Fucose","Myristic acid","Pyrophosphate","Uridine","Hypoxanthine","L-Homocysteic acid","(R)-lipoic acid","Adipic acid","Gluconolactone","Adrenic acid","2,6-Pyridinedicarboxylic acid","2-Keto-3-deoxy-D-gluconic acid","2-Oxovaleric acid","ESCULETIN","3,7-Dimethyluric acid","Isocitric acid","3-Hydroxymethylglutaric acid","(9xi,10xi,12xi)-9,10-Dihydroxy-12-octadecenoic acid","Quinolinic acid","o-Cresol","13-OxoODE","Succinic?acid","L-Pyroglutamic?acid","Indole-3-acetic acid","Dihydroresveratrol","Adenine","Prostaglandin B1","Neotame","Oxoadipic acid","Cortisone","L-Tyrosine","(10E,12Z)-(9S)-9-Hydroperoxyoctadeca-10,12-dienoic acid","L-Serine","Purine","Benzoic acid","3-Hydroxycinnamic acid","L-Rhamnose","4-Hydroxyphenylpyruvate","Kynurenic?acid","Methylsuccinic acid","Beta-D-Galactose","Cholic acid","Arachidonic acid","Protocatechuic acid","3,4,5-trihydroxycyclohex-1-ene-1-carboxylic acid","p-Cresol glucuronide","Cortexolone","LysoPE(18:1(9Z)/0:0)","Cirsiliol","Taurocholic acid","L-Ribulose","2-Isopropylmalic acid","2-Ketobutyric acid","N-Formyl-L-methionine","Maltotriose","Urocanic acid","L-Methionine","N-Formyl-L-aspartate","D-Arabinose","Docosapentaenoic acid (22n-3)","Galabiose","9,10-epoxyoctadecanoic acid","Succinic anhydride","Suberic acid","Erythrono-1,4-lactone","N-methyl-L-glutamic Acid","N,N'-diacetylchitobiose","Picolinic acid","Succinic acid semialdehyde","4-Hydroxy-3-methylbenzoic acid","N-Acetylserine","Linoelaidic acid","Pimelic acid","3-Methyl-2-oxovaleric acid","2,2-Dimethylsuccinic acid","Xanthine","Mesylate","6-Ketoprostaglandin E1","5-Methoxysalicylic acid","Citric acid","trans-Ferulic acid","DL-Dopa","Quinic acid","Gingerol","Aesculin","N-Acetyl-L-alanine","Bilobalide A","8-iso-15-keto-PGE2","Maleamic acid","N-Acetylmuramate","Tiglic acid","Tauroursodeoxycholic acid","Thymidine","Ursodeoxycholic acid","3-Hydroxysebacic acid","Itaconic acid","Methylmalonic acid","L-Alanine","Maleic acid","Malic acid","Stearic acid","S-Nitrosoglutathione","Mercaptopurine","6-Hydroxynicotinic acid","Poncirin","2-Furoic acid","Adrenochrome","2-Hydroxy-3-methylbutyric acid","8-Hydroxy-deoxyguanosine","Phloretic acid","Chorismate","Acetaminophen glucuronide","3-Methyl-2-oxopentanoate","Genistein","3-Hydroxyisovaleric acid","3,4-Dihydroxyhydrocinnamic acid","Pyrrolidonecarboxylic acid","Taurochenodeoxycholate","Hydrocortisone","4-Hydroxyphenylpyruvic acid","4-Aminohippuric?acid","Azelaic acid","L-2-Hydroxyglutaric acid","Hydrogen phosphate","Chrysophanol","Polydatin","2',4',6'-Trihydroxyacetophenone","5-Hydroxyindoleacetate","Pelargonic acid","Deoxycholic acid","Estrone-3-glucuronide","Erythrulose","PGD2 ethanolamide","Isonicotinic acid"],"pubmed_abstract":["Osteosarcoma (OS), a malignant bone tumor with limited treatment options, exhibits low sensitivity to immune checkpoint therapy (ICT). Through genomics and transcriptomics analyses, we identify a subgroup of OS with methylthioadenosine phosphorylase (MTAP) deletion, which contributes to ICT resistance, leading to a \"cold\" tumor microenvironment. MTAP-deleted OS relies on methionine metabolism and is sensitive to methionine intervention, achieved through either dietary restriction or inhibition of methionine adenosyltransferase 2a (MAT2A), a key enzyme in methionine metabolism. We further demonstrate that methionine intervention triggers programmed death-ligand 1 (PD-L1) transcription factor IKAROS family zinc finger 1 (IKZF1) and enhances PD-L1 expression in MTAP-deleted OS cells. Methionine intervention also activates the immune-related signaling pathways in MTAP-deleted OS cells and attracts CD8+ T cells, thereby enhancing the efficacy of ICT. Combining methionine intervention with ICT provides a significant survival benefit in MTAP-deleted OS murine models, suggesting a rationale for combination regimens in OS ICT."],"pubmed_title":["Methionine intervention induces PD-L1 expression to enhance the immune checkpoint therapy response in MTAP-deleted osteosarcoma."],"pubmed_authors":["Mu Haoran H, Zhang Qi Q, Zuo Dongqing D, Wang Jinzeng J, Tao Yining Y, Li Zhen Z, He Xin X, Meng Huanliang H, Wang Hongsheng H, Shen Jiakang J, Sun Mengxiong M, Jiang Yafei Y, Zhao Weisong W, Han Jing J, Yang Mengkai M, Wang Zhuoying Z, Lv Yu Y, Yang Yuqin Y, Xu Jing J, Zhang Tao T, Yang Liu L, Lin Jun J, Tang Feng F, Tang Renhong R, Hu Haiyan H, Cai Zhengdong Z, Sun Wei W, Hua Yingqi Y"],"additional_accession":[]},"is_claimable":false,"name":"Methionine Intervention Induces PD-L1 Expression to Enhance the Immune Checkpoint Therapy Response in MTAP-deleted Osteosarcoma","description":"Osteosarcoma (OS), a malignant bone tumor with limited treatment options, exhibits low sensitivity to immune checkpoint therapy (ICT). Through genomics and transcriptomics analyses, we have identified a subgroup of OS with methylthioadenosine phosphorylase (MTAP) deletion, which contributes to ICT resistance, leading to a 'cold' tumor microenvironment. MTAP-deleted OS relies on methionine metabolism, and is sensitive to methionine intervention, achieved either through dietary restriction or inhibition of methionine adenosyltransferase 2a (MAT2A), a key enzyme in methionine metabolism. We have further demonstrated that methionine intervention triggers PD-L1 transcription factor IKAROS family zinc finger 1 (IKZF1) and enhances PD-L1 expression in MTAP-deleted OS cells. Methionine intervention also activates the immune-related signaling pathways in MTAP-deleted OS cells and attracts CD8+ T cells, thereby enhancing the efficacy of ICT. Combining methionine intervention with ICT provides a significant survival benefit in MTAP-deleted OS murine models, suggesting a rationale for combination regimens in OS ICT.","dates":{"publication":"2026-06-09","submission":"2026-06-09"},"accession":"MTBLS11985","cross_references":{"MetaboLights":["MTBLC192304","MTBLC167175","MTBLC229942","MTBLC173341","MTBLC53492"],"pubmed":["39983717"],"ChEBI":["CHEBI:192304","CHEBI:167175","CHEBI:229942","CHEBI:173341","CHEBI:53492"]}}