Metabolome Profiling of Malignant Ascites Identifies Candidate Metabolic Biomarkers of Hepatocellular Carcinoma


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Background:Malignant ascites is one of the severe complications of hepatocellular carcinoma, which can be regarded as a unique tumor microenvironment of hepatocellular carcinoma. The identification of novel biomarkers in malignant ascites could be crucial to differentiate patients with hepatocellular carcinoma and cirrhotic ascites.

Objective:The study aimed to distinguish the metabolomics of malignant ascites in patients with hepatocellular carcinoma from that of non-malignant ascites (cirrhotic ascites).

Methods:Liquid chromatography-mass spectrometry was performed to analyze the differentially distributed biomarkers in patients with malignant ascites and hepatocellular carcinoma (n = 39), as well as in patients with cirrhotic ascites, which were taken as controls (n = 36).

Results:Our results suggest that the key factors associated with pathways, such as arachidonic acid, phenylalanine, and glutamic acid pathways, are potential ascitic fluidbased biomarkers for differentiating hepatocellular carcinoma with cirrhosis ascites; the results also provide a clinical pathophysiological interpretation of biomarkers and metabolic pathways relevant to disease status.

Conclusion:Our results suggest that the key factors associated with pathways, such as arachidonic acid, phenylalanine, and glutamic acid pathways, are potential ascitic fluidbased biomarkers for differentiating hepatocellular carcinoma with cirrhosis ascites; the results also provide a clinical pathophysiological interpretation of biomarkers and metabolic pathways relevant to disease status.

Об авторах

Weijia Wang

Department of International Medical Services (IMS), Beijing Tiantan Hospital of Capital Medical University

Email: info@benthamscience.net

Yue Wu

Department of International Medical Services (IMS), Beijing Tiantan Hospital of Capital Medical University

Email: info@benthamscience.net

Qinsheng Zhang

Department of Hepatobiliary Spleen and Gastroenterology,, Henan Provincial Hospital of Traditional Chinese Medicine, Henan University of Chinese Medicine

Автор, ответственный за переписку.
Email: info@benthamscience.net

Peilin Cui

Department of International Medical Services (IMS), Beijing Tiantan Hospital of Capital Medical University

Автор, ответственный за переписку.
Email: info@benthamscience.net

Список литературы

  1. Zheng, L.; Xu, M.; Xu, J.; Wu, K.; Fang, Q.; Liang, Y.; Zhou, S.; Cen, D.; Ji, L.; Han, W.; Cai, X. ELF3 promotes epithelial–mesenchymal transition by protecting ZEB1 from miR-141-3p-mediated silencing in hepatocellular carcinoma. Cell Death Dis., 2018, 9(3), 387. doi: 10.1038/s41419-018-0399-y PMID: 29523781
  2. El-Serag, H.B. Hepatocellular carcinoma. N. Engl. J. Med., 2011, 365(12), 1118-1127. doi: 10.1056/NEJMra1001683 PMID: 21992124
  3. Pavlova, N.N.; Thompson, C.B. The emerging hallmarks of cancer metabolism. Cell Metab., 2016, 23(1), 27-47. doi: 10.1016/j.cmet.2015.12.006 PMID: 26771115
  4. Cavazzoni, E.; Bugiantella, W.; Graziosi, L.; Franceschini, M.S.; Donini, A. Malignant ascites: Pathophysiology and treatment. Int. J. Clin. Oncol., 2013, 18(1), 1-9. doi: 10.1007/s10147-012-0396-6 PMID: 22460778
  5. Watala, C.; Karolczak, K.; Kassassir, H.; Talar, M.; Przygodzki, T.; Maczynska, K.; Labieniec-Watala, M. How do the full-generation poly(amido)amine (PAMAM) dendrimers activate blood platelets? Activation of circulating platelets and formation of "fibrinogen aggregates" in the presence of polycations. Int. J. Pharm., 2016, 503(1-2), 247-261. doi: 10.1016/j.ijpharm.2015.08.073 PMID: 26319628
  6. Pillai, R.C.; Fraser, J.F.; Ziegenfuss, M.; Bhaskar, B. Influence of circulating levels of fibrinogen and perioperative coagulation parameters on predicting postoperative blood loss in cardiac surgery: A prospective observational study. J. Card. Surg., 2014, 29(2), 189-195. doi: 10.1111/jocs.12255 PMID: 24734282
  7. Moore, C.M.; Van Thiel, D.H. Cirrhotic ascites review: Pathophysiology, diagnosis and management. World J. Hepatol., 2013, 5(5), 251-263. doi: 10.4254/wjh.v5.i5.251 PMID: 23717736
  8. Oberg, A.L.; Mahoney, D.W. Statistical methods for quantitative mass spectrometry proteomic experiments with labeling. BMC Bioinformatics, 2012, 13(S16), 7. doi: 10.1186/1471-2105-13-S16-S7
  9. Thompson, J.W.; Forrester, M.T.; Moseley, M.A.; Foster, M.W. Solid-phase capture for the detection and relative quantification of S-nitrosoproteins by mass spectrometry. Methods, 2013, 62(2), 130-137. doi: 10.1016/j.ymeth.2012.10.001 PMID: 23064468
  10. Mehrotra, S.; Goyal, V. Evaluation of designer crops for biosafety-A scientist’s perspective. Gene, 2013, 515(2), 241-248. doi: 10.1016/j.gene.2012.12.029 PMID: 23266812
  11. Sauzay, C.; Petit, A.; Bourgeois, A.M.; Barbare, J.C.; Chauffert, B.; Galmiche, A.; Houessinon, A. Alpha-foetoprotein (AFP): A multi-purpose marker in hepatocellular carcinoma. Clin Chim Acta, 2016, 463, 39-44.
  12. Lindon, J.C.; Holmes, E.; Nicholson, J.K. Metabonomics in pharmaceutical R & D. FEBS J., 2007, 274(5), 1140-1151. doi: 10.1111/j.1742-4658.2007.05673.x PMID: 17298438
  13. Zhang, J.; Liang, R.; Wei, J.; Ye, J.; He, Q.; ChunlingYuan; Ye, J.; Li, Y.; Liu, Z.; Lin, Y. Identification of candidate biomarkers in malignant ascites from patients with hepatocellular carcinoma by iTRAQ-based quantitative proteomic analysis. BioMed Res. Int., 2018, 2018, 1-11. doi: 10.1155/2018/5484976 PMID: 30345303
  14. Lee, S.S.; Min, H.J.; Choi, J.Y.; Cho, H.C.; Kim, J.J.; Lee, J.M.; Kim, H.J.; Ha, C.Y.; Kim, H.J.; Kim, T.H.; Kim, J.H.; Lee, O.J. Usefulness of ascitic fluid lactoferrin levels in patients with liver cirrhosis. BMC Gastroenterol., 2016, 16(1), 132. doi: 10.1186/s12876-016-0546-9 PMID: 27733127
  15. Sui, Z.; Li, Q.; Zhu, L.; Wang, Z.; Lv, C.; Liu, R.; Xu, H.; He, B.; Li, Z.; Bi, K. An integrative investigation of the toxicity of Aconiti kusnezoffii radix and the attenuation effect of its processed drug using a UHPLC-Q-TOF based rat serum and urine metabolomics strategy. J. Pharm. Biomed. Anal., 2017, 145, 240-247. doi: 10.1016/j.jpba.2017.06.049 PMID: 28668652
  16. Wang, X.; Zhang, A.; Sun, H. Power of metabolomics in diagnosis and biomarker discovery of hepatocellular carcinoma. Hepatology, 2013, 57(5), 2072-2077. doi: 10.1002/hep.26130 PMID: 23150189
  17. Jiang, M.; Lu, C.; Zhang, C.; Yang, J.; Tan, Y.; Lu, A.; Chan, K. Syndrome differentiation in modern research of traditional Chinese medicine. J. Ethnopharmacol., 2012, 140(3), 634-642. doi: 10.1016/j.jep.2012.01.033 PMID: 22322251
  18. Zira, A.N.; Theocharis, S.E.; Mitropoulos, D.; Migdalis, V.; Mikros, E. (1)H NMR metabonomic analysis in renal cell carcinoma: A possible diagnostic tool. J. Proteome Res., 2010, 9(8), 4038-4044. doi: 10.1021/pr100226m PMID: 20527959
  19. Lu, X.; Zhao, X.; Bai, C.; Zhao, C.; Lu, G.; Xu, G. LC–MS-based metabonomics analysis. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2008, 866(1-2), 64-76. doi: 10.1016/j.jchromb.2007.10.022 PMID: 17983864
  20. Jiang, W.; Qiu, Y.; Ni, Y.; Su, M.; Jia, W.; Du, X. An automated data analysis pipeline for GC-TOF-MS metabonomics studies. J. Proteome Res., 2010, 9(11), 5974-5981. doi: 10.1021/pr1007703 PMID: 20825247
  21. Safaei, A.; Arefi Oskouie, A.; Mohebbi, S.R.; Rezaei-Tavirani, M.; Mahboubi, M.; Peyvandi, M.; Okhovatian, F.; Zamanian-Azodi, M. Metabolomic analysis of human cirrhosis, hepatocellular carcinoma, non-alcoholic fatty liver disease and non-alcoholic steatohepatitis diseases. Gastroenterol. Hepatol. Bed Bench, 2016, 9(3), 158-173. PMID: 27458508
  22. Cui, W.; Zhang, J.; Wu, D.; Zhang, J.; Zhou, H.; Rong, Y.; Liu, F.; Wei, B.; Xu, X. Ponicidin suppresses pancreatic cancer growth by inducing ferroptosis: Insight gained by mass spectrometry-based metabolomics. Phytomedicine, 2022, 98, 153943. doi: 10.1016/j.phymed.2022.153943 PMID: 35104766
  23. Zhang, H.; Bian, S.; Xu, Z.; Gao, M.; Wang, H.; Zhang, J.; Zhang, M.; Ke, Y.; Wang, W.; Chen, Z.S.; Xu, H. The effect and mechanistic study of encequidar on reversing the resistance of SW620/AD300 cells to doxorubicin. Biochem. Pharmacol., 2022, 205, 115258. doi: 10.1016/j.bcp.2022.115258 PMID: 36179932
  24. Jha, V.K.; Shenoy, G.; Borpujari, P.J.; Banerjee, M. Biomarkers of malignant ascites-a myth or reality. Med. J. Armed Forces India, 2011, 67(4), 398. doi: 10.1016/S0377-1237(11)60100-7 PMID: 27365864
  25. Coloff, J.L.; Murphy, J.P.; Braun, C.R.; Harris, I.S.; Shelton, L.M.; Kami, K.; Gygi, S.P.; Selfors, L.M.; Brugge, J.S. Differential glutamate metabolism in proliferating and quiescent mammary epithelial cells. Cell Metab., 2016, 23(5), 867-880. doi: 10.1016/j.cmet.2016.03.016 PMID: 27133130
  26. Prickett, T.D.; Samuels, Y. Molecular pathways: Dysregulated glutamatergic signaling pathways in cancer. Clin. Cancer Res., 2012, 18(16), 4240-4246. doi: 10.1158/1078-0432.CCR-11-1217 PMID: 22648273
  27. Matsuda, K. Novel susceptibility loci for hepatocellular carcinoma in chronic HBV carriers. Hepatobiliary Surg. Nutr., 2012, 1(1), 59-60. PMID: 24570905
  28. Nahon, P.; Amathieu, R.; Triba, M.N.; Bouchemal, N.; Nault, J.C.; Ziol, M.; Seror, O.; Dhonneur, G.; Trinchet, J.C.; Beaugrand, M.; Le Moyec, L. Identification of serum proton NMR metabolomic fingerprints associated with hepatocellular carcinoma in patients with alcoholic cirrhosis. Clin. Cancer Res., 2012, 18(24), 6714-6722. doi: 10.1158/1078-0432.CCR-12-1099 PMID: 23136190
  29. Han, M.; Xie, M.; Han, J.; Yuan, D.; Yang, T.; Xie, Y. Development and validation of a rapid, selective, and sensitive LC–MS/MS method for simultaneous determination of d- and l-amino acids in human serum: application to the study of hepatocellular carcinoma. Anal. Bioanal. Chem., 2018, 410(10), 2517-2531. doi: 10.1007/s00216-018-0883-3 PMID: 29492623
  30. Keshet, R.; Szlosarek, P.; Carracedo, A.; Erez, A. Rewiring urea cycle metabolism in cancer to support anabolism. Nat. Rev. Cancer, 2018, 18(10), 634-645. doi: 10.1038/s41568-018-0054-z PMID: 30194362
  31. Kim, D.; Cho, E.; Yu, K.S.; Jang, I.J.; Yoon, J.H.; Park, T.; Cho, J.Y. Comprehensive metabolomic search for biomarkers to differentiate early stage hepatocellular carcinoma from cirrhosis. Cancers, 2019, 11(10), 1497. doi: 10.3390/cancers11101497 PMID: 31590436
  32. Spinelli, J.B.; Yoon, H.; Ringel, A.E.; Jeanfavre, S.; Clish, C.B.; Haigis, M.C. Metabolic recycling of ammonia via glutamate dehydrogenase supports breast cancer biomass. Science, 2017, 358(6365), 941-946. doi: 10.1126/science.aam9305 PMID: 29025995
  33. Brosnan, M.E.; Brosnan, J.T. Hepatic glutamate metabolism: A tale of 2 hepatocytes. Am. J. Clin. Nutr., 2009, 90(3), 857S-861S. doi: 10.3945/ajcn.2009.27462Z PMID: 19625684
  34. Mian, A.; Lee, B. Urea-cycle disorders as a paradigm for inborn errors of hepatocyte metabolism. Trends Mol. Med., 2002, 8(12), 583-589. doi: 10.1016/S1471-4914(02)02437-1 PMID: 12470992
  35. Gong, Z.G.; Zhao, W.; Zhang, J.; Wu, X.; Hu, J.; Yin, G.C.; Xu, Y.J. Metabolomics and eicosanoid analysis identified serum biomarkers for distinguishing hepatocellular carcinoma from hepatitis B virus-related cirrhosis. Oncotarget, 2017, 8(38), 63890-63900. doi: 10.18632/oncotarget.19173 PMID: 28969038
  36. Yang, F.; Li, J.; Deng, H.; Wang, Y.; Lei, C.; Wang, Q.; Xiang, J.; Liang, L.; Xia, J.; Pan, X.; Li, X.; Long, Q.; Chang, L.; Xu, P.; Huang, A.; Wang, K.; Tang, N. GSTZ 1-1 deficiency activates NRF 2/ IGF 1R Axis in HCC via accumulation of oncometabolite succinylacetone. EMBO J., 2019, 38(15), e101964. doi: 10.15252/embj.2019101964 PMID: 31267557
  37. Linkous, A.G.; Yazlovitskaya, E.M.; Hallahan, D.E. Cytosolic phospholipase A2 and lysophospholipids in tumor angiogenesis. J. Natl. Cancer Inst., 2010, 102(18), 1398-1412. doi: 10.1093/jnci/djq290 PMID: 20729478
  38. Jee, S.H.; Kim, M.; Kim, M.; Yoo, H.J.; Kim, H.; Jung, K.J.; Hong, S.; Lee, J.H. Metabolomics profiles of hepatocellular carcinoma in a Korean prospective cohort: The Korean cancer prevention study-II. Cancer Prev. Res. (Phila.), 2018, 11(5), 303-312. doi: 10.1158/1940-6207.CAPR-17-0249 PMID: 29500188
  39. Sun, X.M.; Dong, W.G.; Yu, B.P.; Luo, H.S.; Yu, J.P. Detection of type IV collagenase activity in malignant ascites. World J. Gastroenterol., 2003, 9(11), 2592-2595. doi: 10.3748/wjg.v9.i11.2592 PMID: 14606104
  40. Kountouras, J.; Boura, P.; Tsapas, G.; Charisis, K.; Magoula, I.; Tsakiri, I. Value of ascitic fluid ferritin in the differential diagnosis of malignant ascites. Anticancer Res., 1993, 13(6B), 2441-2445. PMID: 8135481
  41. Wang, X.; Lin, G.; Huang, Y. Study on biomarkers of serum and ascites in patients with liver cirrhosis or liver cancer. World Chin. Digestion J., 1999, 7, 642-643.
  42. Xu, P.; Zhu, B. Clinical significance of serum and ascites α-L-fucosylase in liver cancer. Jiangsu Med., 1990, 16(2), 91-92.

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