Serum metabolic effects of corn oligopeptides with 7-day supplementation on early post-surgery primary liver cancer patients: a double-blind randomized controlled trial

Weiqi Rong, Hui Xia, Kai Zhang, Yihan Zhang, Changcheng Tao, Fan Wu, Liming Wang, Hong Zhang, Guiju Sun, Jianxiong Wu, Weiqi Rong, Hui Xia, Kai Zhang, Yihan Zhang, Changcheng Tao, Fan Wu, Liming Wang, Hong Zhang, Guiju Sun, Jianxiong Wu

Abstract

Background: Liver cancer as the main leading cancer has caused heavy burdens globally. The prognosis of liver cancer is closely related with postoperative nutrition support. Corn oligopeptides (COPs) are protein hydrolysates produced by enzymatic treatments, which have shown potential bioactivities, such as inhibiting angiotensin I-converting enzyme, resisting lipid peroxidation and anti-oxidant. However, the correlation between COPs and liver cancer patients is still unknown and the potential mechanism of COPs on liver cancer is unclear as well. The aim of this study was to assess effects of 7-day intervention of COPs after surgery on liver function and serum metabolic profiles of liver cancer patients.

Methods: Patients were assigned into COPs intervention group (n=50) and control group (n=91) for 7 days. Investigations were scheduled at 1st day and 7th day after liver resection surgery respectively, mainly including anthropometric, biochemical indexes and liquid chromatography-mass spectrometry (LC/MS) analysis.

Results: Seven-day supplementation of COPs on early post-surgery liver cancer patients down-regulated levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin and up-regulated prothrombin time activity and prealbumin levels. LC/MS analysis revealed metabolic signatures including regulation of 16 metabolites, which was closely related with two metabolic pathways (nicotinate and nicotinamide metabolism, fatty acid metabolism).

Conclusions: COPs supplementation has displayed the potentials on alleviating the injury of liver function and it may be due to regulation of fatty acid metabolism, nicotinate and nicotinamide metabolism, lipid peroxidation and anti-inflammatory action. More researches are warranted in future to confirm the exact mechanisms.

Keywords: Liver cancer; corn oligopeptides supplementation; metabolomics; randomized controlled trial.

Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-21-116/coif). The authors report support from National Key Research and Development Program of China (No. 2016YFD0400604) and have no other conflicts of interest to declare.

2022 Hepatobiliary Surgery and Nutrition. All rights reserved.

Figures

Figure 1
Figure 1
Participant flow throughout the study. TI, corn oligopeptides intervention group; CI, control group.
Figure 2
Figure 2
COPs intervention in patients affects the serum metabolome. The PCA score plots of total serum samples. TGBSS, treatment group before surgery in serum; CGBSS, control group before surgery in serum; TGASS, treatment group after surgery for 7 days in serum; CGASS, control group after surgery for 7 days in serum; QC, quality control; COPs, corn oligopeptides; PCA, principal component analysis.
Figure 3
Figure 3
COPs intervention in patients affects the serum metabolome. The PCA (left) and OPLS-DA (right) score plots of serum. TGBSS, treatment group before surgery in serum; CGBSS, control group before surgery in serum; TGASS, treatment group after surgery for 7 days in serum; CGASS, control group after surgery for 7 days in serum; QC, quality control; COPs, corn oligopeptides; PCA, principal component analysis; OPLS-DA, orthogonal projections to latent structures-discriminant analysis.
Figure 4
Figure 4
COPs intervention in patients affects the serum metabolome. Permutation test charts for OPLS-DA model of serum samples between TA and CA. TA, treatment group after surgery for 7 days in serum; CA, control group after surgery for 7 days in serum; COPs, corn oligopeptides; OPLS-DA, orthogonal projections to latent structures-discriminant analysis.
Figure 5
Figure 5
Pathway impact prediction of KEGG online database between TA and CA. The results of metabolic pathway analysis are presented in bubble diagram. The P value of enrichment analysis [negative natural logarithm, i.e., -ln(P)] positively correlated with the bubble color depth. TA, treatment group after surgery for 7 days in serum; CA, control group after surgery for 7 days in serum; KEGG, Kyoto Encyclopedia of Genes and Genomes.
Figure 6
Figure 6
Correlation analysis between metabolites and serum indexes. Red (corr =1), blue (corr =−1), white (corr =0) and, * represents a significant correlation (P

References

    1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394-424. 10.3322/caac.21492
    1. Global Burden of Disease Cancer Collaboration ; Fitzmaurice C, Abate D, et al. Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2017: A Systematic Analysis for the Global Burden of Disease Study. JAMA Oncol 2019;5:1749-68. 10.1001/jamaoncol.2019.2996
    1. Zhou J, Sun HC, Wang Z, et al. Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China (2017 Edition). Liver Cancer 2018;7:235-60. 10.1159/000488035
    1. Global Burden of Disease Liver Cancer Collaboration ; Akinyemiju T, Abera S, et al. The Burden of Primary Liver Cancer and Underlying Etiologies From 1990 to 2015 at the Global, Regional, and National Level: Results From the Global Burden of Disease Study 2015. JAMA Oncol 2017;3:1683-91. 10.1001/jamaoncol.2017.3055
    1. Oh SE, Choi MG, Seo JM, et al. Prognostic significance of perioperative nutritional parameters in patients with gastric cancer. Clin Nutr 2019;38:870-6. 10.1016/j.clnu.2018.02.015
    1. Rinninella E, Fagotti A, Cintoni M, et al. Nutritional Interventions to Improve Clinical Outcomes in Ovarian Cancer: A Systematic Review of Randomized Controlled Trials. Nutrients 2019;11:1404. 10.3390/nu11061404
    1. Yan X, Liu L, Zhang Y, et al. Perioperative Enteral Nutrition Improves Postoperative Recovery for Patients with Primary Liver Cancer: A Randomized Controlled Clinical Trial. Nutr Cancer 2021;73:1924-32. 10.1080/01635581.2020.1814824
    1. Zhou Y, Li Y, Zhou T, et al. Dietary Natural Products for Prevention and Treatment of Liver Cancer. Nutrients 2016;8:156. 10.3390/nu8030156
    1. Ren Y, Yang Y, Wu W, et al. Identification and characterization of novel anticoagulant peptide with thrombolytic effect and nutrient oligopeptides with high branched chain amino acid from Whitmania pigra protein. Amino Acids 2016;48:2657-70. 10.1007/s00726-016-2299-8
    1. Suarez-Jimenez GM, Burgos-Hernandez A, Ezquerra-Brauer JM. Bioactive peptides and depsipeptides with anticancer potential: sources from marine animals. Mar Drugs 2012;10:963-86. 10.3390/md10050963
    1. Ganguly A, Sharma K, Majumder K. Food-derived bioactive peptides and their role in ameliorating hypertension and associated cardiovascular diseases. Adv Food Nutr Res 2019;89:165-207. 10.1016/bs.afnr.2019.04.001
    1. Fernández-Tomé S, Marin AC, Ortega Moreno L, et al. Immunomodulatory Effect of Gut Microbiota-Derived Bioactive Peptides on Human Immune System from Healthy Controls and Patients with Inflammatory Bowel Disease. Nutrients 2019;11:2605. 10.3390/nu11112605
    1. Zhang F, Zhang J, Li Y. Corn oligopeptides protect against early alcoholic liver injury in rats. Food Chem Toxicol 2012;50:2149-54. 10.1016/j.fct.2012.03.083
    1. Lin F, Chen L, Liang R, et al. Pilot-scale production of low molecular weight peptides from corn wet milling byproducts and the antihypertensive effects in vivo and in vitro. Food Chemistry 2011;124:801-7. 10.1016/j.foodchem.2010.06.099
    1. Zhou C, Hu J, Ma H, et al. Antioxidant peptides from corn gluten meal: Orthogonal design evaluation. Food Chem 2015;187:270-8. 10.1016/j.foodchem.2015.04.092
    1. Li HM, Hu XIN, Guo P, et al. Antioxidant properties and possible mode of action of corn protein peptides and zein peptides. J Food Biochem 2010;34:44-60. 10.1111/j.1745-4514.2009.00292.x
    1. Yamaguchi M, Nishikiori F, Ito M, et al. The effects of corn peptide ingestion on facilitating alcohol metabolism in healthy men. Biosci Biotechnol Biochem 1997;61:1474-81. 10.1271/bbb.61.1474
    1. Yu Y, Wang L, Wang Y, et al. Hepatoprotective Effect of Albumin Peptides from Corn Germ Meal on Chronic Alcohol-Induced Liver Injury in Mice. J Food Sci 2017;82:2997-3004. 10.1111/1750-3841.13953
    1. She X, Wang F, Ma J, et al. In vitro antioxidant and protective effects of corn peptides on ethanol-induced damage in HepG2 cells. Food and Agricultural Immunology 2016;27:99-110. 10.1080/09540105.2015.1079597
    1. Jones DP, Park Y, Ziegler TR. Nutritional metabolomics: progress in addressing complexity in diet and health. Annu Rev Nutr 2012;32:183-202. 10.1146/annurev-nutr-072610-145159
    1. Gibbons H, O'Gorman A, Brennan L. Metabolomics as a tool in nutritional research. Curr Opin Lipidol 2015;26:30-4. 10.1097/MOL.0000000000000140
    1. Gibney MJ, Walsh M, Brennan L, et al. Metabolomics in human nutrition: opportunities and challenges. Am J Clin Nutr 2005;82:497-503. 10.1093/ajcn/82.3.497
    1. Moazzami AA, Bondia-Pons I, Hanhineva K, et al. Metabolomics reveals the metabolic shifts following an intervention with rye bread in postmenopausal women--a randomized control trial. Nutr J 2012;11:88. 10.1186/1475-2891-11-88
    1. Zheng JS, Lin M, Imamura F, et al. Serum metabolomics profiles in response to n-3 fatty acids in Chinese patients with type 2 diabetes: a double-blind randomised controlled trial. Sci Rep 2016;6:29522. 10.1038/srep29522
    1. Cong WM, Bu H, Chen J, et al. Practice guidelines for the pathological diagnosis of primary liver cancer: 2015 update. World J Gastroenterol 2016;22:9279-87. 10.3748/wjg.v22.i42.9279
    1. Mohammadi E, Tamaddoni A, Qujeq D, et al. An investigation of the effects of curcumin on iron overload, hepcidin level, and liver function in β-thalassemia major patients: A double-blind randomized controlled clinical trial. Phytother Res 2018;32:1828-35. 10.1002/ptr.6118
    1. Panahi Y, Kianpour P, Mohtashami R, et al. Efficacy of artichoke leaf extract in non-alcoholic fatty liver disease: A pilot double-blind randomized controlled trial. Phytother Res 2018;32:1382-7. 10.1002/ptr.6073
    1. Xiong X, Ren Y, Cui Y, et al. Obeticholic acid protects mice against lipopolysaccharide-induced liver injury and inflammation. Biomed Pharmacother 2017;96:1292-8. 10.1016/j.biopha.2017.11.083
    1. Liu X, Cao L, Zhang T, et al. Effect of Remote Ischemic Preconditioning in Patients Undergoing Hepatectomy With Portal Triad Clamping: A Randomized Controlled Trial. Anesth Analg 2019;129:1742-8. 10.1213/ANE.0000000000004434
    1. Zheng ZJ, Fu J, Zhi F, et al. The effects of interventional therapy on serum HTATIP2/TIP30, B7-H4 and short-term curative effect in primary hepatocellular carcinoma. Eur Rev Med Pharmacol Sci 2018;22:6778-83.
    1. Gong Y, Liu Z, Liao Y, et al. Effectiveness of ω-3 Polyunsaturated Fatty Acids Based Lipid Emulsions for Treatment of Patients after Hepatectomy: A Prospective Clinical Trial. Nutrients 2016;8:357. 10.3390/nu8060357
    1. Shi M, Zhang Z, Xu R, et al. Human mesenchymal stem cell transfusion is safe and improves liver function in acute-on-chronic liver failure patients. Stem Cells Transl Med 2012;1:725-31. 10.5966/sctm.2012-0034
    1. Aksoy S, Szumlanski CL, Weinshilboum RM. Human liver nicotinamide N-methyltransferase. cDNA cloning, expression, and biochemical characterization. J Biol Chem 1994;269:14835-40. 10.1016/S0021-9258(17)36700-5
    1. Sternak M, Khomich TI, Jakubowski A, et al. Nicotinamide N-methyltransferase (NNMT) and 1-methylnicotinamide (MNA) in experimental hepatitis induced by concanavalin A in the mouse. Pharmacol Rep 2010;62:483-93. 10.1016/S1734-1140(10)70304-2
    1. Hong S, Moreno-Navarrete JM, Wei X, et al. Nicotinamide N-methyltransferase regulates hepatic nutrient metabolism through Sirt1 protein stabilization. Nat Med 2015;21:887-94. 10.1038/nm.3882
    1. Taniki N, Nakamoto N, Chu PS, et al. Intestinal barrier regulates immune responses in the liver via IL-10-producing macrophages. JCI Insight 2018. 10.1172/jci.insight.91980
    1. Watanabe H, Kobayashi A, Hayashi H, et al. Effects of long-chain acyl carnitine on membrane fluidity of human erythrocytes. Biochim Biophys Acta 1989;980:315-8. 10.1016/0005-2736(89)90318-0
    1. Wang C, Feng R, Li Y, et al. The metabolomic profiling of serum in rats exposed to arsenic using UPLC/Q-TOF MS. Toxicol Lett 2014;229:474-81. 10.1016/j.toxlet.2014.06.001
    1. Jee SH, Kim M, Kim M, et al. Metabolomics Profiles of Hepatocellular Carcinoma in a Korean Prospective Cohort: The Korean Cancer Prevention Study-II. Cancer Prev Res (Phila) 2018;11:303-12. 10.1158/1940-6207.CAPR-17-0249
    1. Liu X, Liu Y, Cheng M, et al. Metabolomic Responses of Human Hepatocytes to Emodin, Aristolochic Acid, and Triptolide: Chemicals Purified from Traditional Chinese Medicines. J Biochem Mol Toxicol 2015;29:533-43. 10.1002/jbt.21724
    1. Khedr AI, Ibrahim SR, Mohamed GA, et al. New ursane triterpenoids from Ficus pandurata and their binding affinity for human cannabinoid and opioid receptors. Arch Pharm Res 2016;39:897-911. 10.1007/s12272-016-0784-y
    1. Burton GW, Foster DO, Perly B, et al. Biological antioxidants. Philos Trans R Soc Lond B Biol Sci 1985;311:565-78. 10.1098/rstb.1985.0164
    1. Horton AA, Fairhurst S. Lipid peroxidation and mechanisms of toxicity. Crit Rev Toxicol 1987;18:27-79. 10.3109/10408448709089856
    1. Hayashi T, Kanetoshi A, Nakamura M, et al. Reduction of alpha-tocopherolquinone to alpha-tocopherolhydroquinone in rat hepatocytes. Biochem Pharmacol 1992;44:489-93. 10.1016/0006-2952(92)90440-T
    1. Bindoli A, Valente M, Cavallini L. Inhibition of lipid peroxidation by alpha-tocopherolquinone and alpha-tocopherolhydroquinone. Biochem Int 1985;10:753-61.
    1. Valenzuela R, Videla LA. Impact of the Co-Administration of N-3 Fatty Acids and Olive Oil Components in Preclinical Nonalcoholic Fatty Liver Disease Models: A Mechanistic View. Nutrients 2020;12:499. 10.3390/nu12020499
    1. Khoury T, Chen S, Abu Rmeileh A, et al. Acute liver injury induced by levetiracetam and temozolomide co-treatment. Dig Liver Dis 2017;49:297-300. 10.1016/j.dld.2016.11.015

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