Monitoring one-carbon metabolism by mass spectrometry to assess liver function and disease
Tóm tắt
Precision medicine promises to overcome the constraints of the traditional “one-for-all” healthcare approach through a clear understanding of the molecular features of a disease, allowing for innovative and tailored treatments. State-of-the-art proteomics has the potential to accurately explore the human proteome to identify, quantify, and characterize proteins associated with disease progression. There is a pressing need for informative biomarkers to diagnose liver disease early in its course to prevent severe disease for which no efficient treatment is yet available. Here, we propose the concept of a cellular pathway as a functional biomarker, whose monitorization may inform normal and pathological status. We have developed a standardized targeted selected-reaction monitoring assay to detect and quantify 13 enzymes of one-carbon metabolism (1CM). The assay is compliant with Clinical Proteomics Tumor Analysis Consortium (CPTAC) guidelines and has been included in the protein quantification assays that can be accessed through the assay portal at the CPTAC web page. To test the feasibility of the assay, we conducted a retrospective, proof-of-concept study on a collection of liver samples from healthy controls and from patients with cirrhosis or hepatocellular carcinoma (HCC). Our results indicate a significant reconfiguration of 1CM upon HCC development resulting from a process that can already be identified in cirrhosis. Our findings indicate that the systematic and integrated quantification of 1CM enzymes is a promising cell function-based biomarker for patient stratification, although further experiments with larger cohorts are needed to confirm these findings.
Tài liệu tham khảo
Altekruse SF, McGlynn KA, Reichman ME (2009) Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005. J Clin Oncol 27(9):1485–1491
Bigaud E, Corrales FJ (2016) Methylthioadenosine (MTA) regulates liver cells proteome and methylproteome: implications in liver biology and disease. Mol Cell Proteomics 15(5):1498–1510
Bosch FX, Ribes J, Díaz M, Cléries R (2004) Primary liver cancer: worldwide incidence and trends. Gastroenterology, 127(5):S5–S16
Carr SA, Abbatiello SE, Ackermann BL et al (2014) Targeted peptide measurements in biology and medicine: best practices for mass spectrometry-based assay development using a fit-for-purpose approach. Mol Cell Proteomics 13:907–917
Chauhan R, Lahiri N (2016) Tissue- and serum-associated biomarkers of hepatocellular carcinoma. Biomark Cancer 8(1):BIC.S34413
Deutsch EW (2010) The PeptideAtlas Project. Methods Mol Biol (Clifton, NJ) 604:285–296
Ebhardt HA, Root A, Sander C, Aebersold R (2015) Applications of targeted proteomics in systems biology and translational medicine. Proteomics 15:3193–3208
El-Serag HB (2007) Translational research: the study of community effectiveness in digestive and liver disorders. Gastroenterology 132:8–10
Farvardin S, Patel J, Khambaty M et al (2017) Patient-reported barriers are associated with lower hepatocellular carcinoma surveillance rates in patients with cirrhosis. Hepatology (Baltimore, MD) 65:875–884
Fitzmaurice C, Allen C, Barber RM et al (2017) Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: a systematic analysis for the global burden of disease study Global Burden of Disease Cancer Collaboration. JAMA Oncol 3:524–548
Gao Y, Wang X, Sang Z, et al (2017) Quantitative proteomics by SWATH-MS reveals sophisticated metabolic reprogramming in hepatocellular carcinoma tissues. Sci Rep 7(1):1–12
Koźmiński P, Halik PK, Chesori R, Gniazdowska E (2020) Overview of dual-acting drug methotrexate in different neurological diseases, autoimmune pathologies and cancers. Int J Mol Sci 21(10):3483
Kusebauch U, Campbell DS, Deutsch EW et al (2016) Human SRMAtlas: a resource of targeted assays to quantify the complete human proteome. Cell 166:766–778
Llovet JM, Villanueva A, Lachenmayer A, Finn RS (2015) Advances in targeted therapies for hepatocellular carcinoma in the genomic era. Nat Rev Clin Oncol 12:408–424
Llovet JM, Zucman-Rossi J, Pikarsky E et al (2016) Hepatocellular carcinoma. Nat Rev Dis Primers 2:16018
Locasale JW (2013) Serine, glycine and one-carbon units: cancer metabolism in full circle. Nat Rev Cancer 13:572–583
Lu SC, Mato JM (2008) S-Adenosylmethionine in cell growth, apoptosis and liver cancer. J Gastroenterol Hepatol 23(Suppl 1):S73–S77
Maldonado LY, Arsene D, Mato JM, Lu SC (2018) Methionine adenosyltransferases in cancers: mechanisms of dysregulation and implications for therapy. Exp Biol Med 243:107–117
Mato JM, Corrales FJ, Lu SC, Avila MA (2002) S-adenosylmethionine: a control switch that regulates liver function. FASEB J 16(1):15–26
Mato JM, Elortza F, Lu SC et al (2018) Liver cancer-associated changes to the proteome: what deserves clinical focus? Expert Rev Proteomics 15(9):749–756
Mora MI, Molina M, Odriozola L, et al (2017) Prioritizing popular proteins in liver cancer: remodelling one-carbon metabolism. J Proteome Res 16(12):4506–4514
Pino LK, Searle BC, Bollinger JG et al (2020) The Skyline ecosystem: informatics for quantitative mass spectrometry proteomics. Mass Spectrom Rev 39:229–244
Raza A, Sood GK (2014) Hepatocellular carcinoma review: current treatment, and evidence-based medicine. World J Gastroenterol 20:4115–4127
Ruiz F, Corrales FJ, Miqueo C, Mato JM (1998) Nitric oxide inactivates rat hepatic methionine adenosyltransferase in vivo by S-nitrosylation. Hepatology 28(4):1051–1057
Ryerson AB, Eheman CR, Altekruse SF et al (2016) Annual report to the nation on the status of cancer, 1975–2012, featuring the increasing incidence of liver cancer. Cancer 122:1312–1337
Santamaría E, Avila MA, Latasa MU, et al (2003) Functional proteomics of nonalcoholic steatohepatitis: mitochondrial proteins as targets of S-adenosylmethionine. Proc Natl Acad Sci U S America 100(6):3065–3070
Sauzay C, Louandre C, Bodeau S et al (2018) Protein biosynthesis, a target of sorafenib, interferes with the unfolded protein response (UPR) and ferroptosis in hepatocellular carcinoma cells. Oncotarget 9:8400–8414
Schulze K, Imbeaud S, Letouzé E et al (2015) Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets. Nat Genet 47:505–511
Torre LA, Bray F, Siegel RL et al (2015) Global cancer statistics, 2012. CA A Cancer J Clin 65:87–108
Uhlén M, Fagerberg L, Hallström BM et al (2015) Tissue-based map of the human proteome. Science 347(6220)
Van Eyk JE, Snyder MP (2019) Precision medicine: role of proteomics in changing clinical management and care. J Proteome Res 18:1–6
Vander Heiden MG, Cantley LC, Thompson CB (2009) Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science (New York, NY) 324:1029–1033
Wang M, Herrmann CJ, Simonovic M et al (2015) Version 4.0 of PaxDb: protein abundance data, integrated across model organisms, tissues, and cell-lines. Proteomics 15:3163–3168
Wang M, Wei K, Qian B et al (2020) HSP70-eIF4G Interaction promotes protein synthesis and cell proliferation in hepatocellular carcinoma. Cancers 12:1–21
Williams R (2006) Global challenges in liver disease. Hepatology (Baltimore, MD) 44:521–526
Younossi Z, Tacke F, Arrese M et al (2019) Global perspectives on nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Hepatology 69:2672–2682