Metabolic profiling of hepatitis B virus‑related hepatocellular carcinoma with diverse differentiation grades

Zhang,Lei; Huang,Ya; Lian,Mingjian; Fan,Zhijuan; Tian,Yaqiong; Wang,Yufan; Kang,Hua; Liu,Shuang; Liu,Shuye; Li,Tong; Shan,Zhongqiang

doi:10.3892/ol.2017.5596

Metabolic profiling of hepatitis B virus‑related hepatocellular carcinoma with diverse differentiation grades

Authors:
- Lei Zhang
- Ya Huang
- Mingjian Lian
- Zhijuan Fan
- Yaqiong Tian
- Yufan Wang
- Hua Kang
- Shuang Liu
- Shuye Liu
- Tong Li
- Zhongqiang Shan
View Affiliations

Affiliations: Tianjin Key Laboratory of Artificial Cell, Artificial Cell Engineering Technology Research Center of Public Health Ministry, Tianjin Third Central Hospital, Tianjin 300170, P.R. China, Clinical Laboratory Department, Chongqing City First People's Hospital of Wanzhou, Chongqing 404040, P.R. China, Clinical Laboratory Department, Third Central Clinical College, Tianjin Medical University, Tianjin 300070, P.R. China, Tianjin Key Laboratory of Artificial Cell, Clinical Laboratory Department, Tianjin Third Central Hospital, Tianjin 300170, P.R. China, Chemical Engineering Institute, Tianjin University, Tianjin 300072, P.R. China
Published online on: January 11, 2017 https://doi.org/10.3892/ol.2017.5596
Pages: 1204-1210
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The most effective diagnostic tool for the majority of hepatocellular carcinoma (HCC) patients is determining the differentiation grade of their tumors. However liver biopsies, which are currently the most effective way of determining tumor differentiation grade, have several limitations. The present study was designed to select serum characteristic metabolites that correlate with the differentiation grades of hepatitis B virus (HBV)‑related HCC, and so could be used in the clinic as a non‑invasive method of differentiating patients with different grades of HCC. A total of 58 patients with HBV‑related HCC were included in the present study, and divided into three groups according to their tumor differentiation grade. A further 20 patients with HBV‑related liver cirrhosis and 19 healthy volunteers were enrolled. Ultra‑performance liquid chromatography‑mass spectrometry was used to analyze endogenous metabolites. Multivariate statistical analysis was used to examine the data using MZmine 2.0 software. The 14 metabolites that were highly correlated with specific differentiation grades of HCC were then selected for additional study. Receiver operator characteristic curve analysis was used to evaluate their clinical value. In total, 5 metabolites were finally identified, including lysophosphatidylcholine (16:0), oleamide, monoglyceride (0:0/15:0/0:0), lysophosphatidylcholine (18:0) and lysophosphatidylcholine [22:5(7Z,10Z,13Z,16Z,19Z)]. All these metabolites exhibited an excellent ability to distinguish different types of HCC with various differentiation grades and the area under the curve of these metabolites was up to 0.942, showing promising clinical value.

View Figures

View References

1	El-Serag HB: Hepatocellular carcinoma. N Engl J Med. 365:1118–1127. 2011. View Article : Google Scholar : PubMed/NCBI
2	Patel M, Shariff MI, Ladep NG, Thillainayagam AV, Thomas HC, Khan SA and Taylor-Robinson SD: Hepatocellular carcinoma: Diagnostics and screening. J Eval Clin Pract. 18:335–342. 2012. View Article : Google Scholar : PubMed/NCBI
3	Liu Y, Hong Z, Tan G, Dong X, Yang G, Zhao L, Chen X, Zhu Z, Lou Z, Qian B, et al: NMR and LC/MS-based global metabolomics to identify serum biomarkers differentiating hepatocellular carcinoma from liver cirrhosis. Int J Cancer. 135:658–668. 2014. View Article : Google Scholar : PubMed/NCBI
4	Qiang L, Huikai L, Butt K, Wang PP and Hao X: Factors associated with disease survival after surgical resection in Chinese patients with hepatocellular carcinoma. World J Surg. 30:439–445. 2006. View Article : Google Scholar : PubMed/NCBI
5	Shah SA, Greig PD, Gallinger S, Cattral MS, Dixon E, Kim RD, Taylor BR, Grant DR and Vollmer CM: Factors associated with early recurrence after resection for hepatocellular carcinoma and outcomes. J Am Coll Surg. 202:275–283. 2006. View Article : Google Scholar : PubMed/NCBI
6	Martins A, Cortez-Pinto H, Marques-Vidal P, Mendes N, Silva S, Fatela N, Glória H, Marinho R, Távora I, Ramalho F and de Moura MC: Treatment and prognostic factors in patients with hepatocellular carcinoma. Liver Int. 26:680–687. 2006. View Article : Google Scholar : PubMed/NCBI
7	Edmondson HA and Steiner PE: Primary carcinoma of the liver: A study of 100 cases among 48,900 necropsies. Cancer. 7:462–503. 1954. View Article : Google Scholar : PubMed/NCBI
8	Stigliano R, Marelli L, Yu D, Davies N, Patch D and Burroughs AK: Seeding following percutaneous diagnostic and therapeutic approaches for hepatocellular carcinoma. What is the risk and the outcome? Seeding risk for percutaneous approach of HCC. Cancer Treat Rev. 33:437–447. 2007. View Article : Google Scholar : PubMed/NCBI
9	Pawlik TM, Gleisner AL, Anders RA, Assumpcao L, Maley W and Choti MA: Preoperative assessment of hepatocellular carcinoma tumor grade using needle biopsy: Implications for transplant eligibility. Ann Surg. 245:435–442. 2007. View Article : Google Scholar : PubMed/NCBI
10	Nicholson JK, Lindon JC and Holmes E: ‘Metabonomics’: Understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data. Xenobiotica. 29:1181–1189. 1999. View Article : Google Scholar : PubMed/NCBI
11	Fiehn O: Metabolomics-the link between genotypes and phenotypes. Plant Mol Biol. 48:155–171. 2002. View Article : Google Scholar : PubMed/NCBI
12	European Association of the Study of the Liver, . 2011 European Association of the Study of the Liver hepatitis C virus clinical practice guidelines. Liver Int. 32:(Suppl 1). 2–8. 2012. View Article : Google Scholar
13	de Bruijne J, Buster EH, Gelderblom HC, Brouwer JT, de Knegt RJ, van Erpecum KJ, Schalm SW, Bakker CM, Zaaijer HL, Janssen HL, et al: Treatment of chronic hepatitis C virus infection-Dutch national guidelines. Neth J Med. 66:311–322. 2008.PubMed/NCBI
14	Pluskal T, Castillo S, Villar-Briones A and Oresic M: MZmine 2: Modular framework for processing, visualizing, and analyzing mass spectrometry-based molecular profile data. BMC Bioinformatics. 11:3952010. View Article : Google Scholar : PubMed/NCBI
15	Trygg J, Holmes E and Lundstedt T: Chemometrics in metabonomics. J Proteome Res. 6:469–479. 2007. View Article : Google Scholar : PubMed/NCBI
16	Eriksson L, Johansson E, Lindgren F, Sjostrom M and Wold S: Megavariate analysis of hierarchical QSAR data. J Comput Aided Mol Des. 16:711–726. 2002. View Article : Google Scholar : PubMed/NCBI
17	Yin P, Wan D, Zhao C, Chen J, Zhao X, Wang W, Lu X, Yang S, Gu J and Xu G: A metabonomic study of hepatitis B-induced liver cirrhosis and hepatocellular carcinoma by using RP-LC and HILIC coupled with mass spectrometry. Mol Biosyst. 5:868–876. 2009. View Article : Google Scholar : PubMed/NCBI
18	Liu SY, Zhang RL, Kang H, Fan ZJ and Du Z: Human liver tissue metabolic profiling research on hepatitis B virus-related hepatocellular carcinoma. World J Gastroenterol. 19:3423–3432. 2013. View Article : Google Scholar : PubMed/NCBI
19	DuBay D, Sandroussi C, Sandhu L, Cleary S, Guba M, Cattral MS, McGilvray I, Ghanekar A, Selzner M, Greig PD and Grant DR: Liver transplantation for advanced hepatocellular carcinoma using poor tumor differentiation on biopsy as an exclusion criterion. Ann Surg. 253:166–172. 2011. View Article : Google Scholar : PubMed/NCBI
20	Yaprak O, Akyildiz M, Dayangac M, Demirbas BT, Guler N, Dogusoy GB, Yuzer Y and Tokat Y: AFP level and histologic differentiation predict the survival of patients with liver transplantation for hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int. 11:256–261. 2012. View Article : Google Scholar : PubMed/NCBI
21	Jiang T, Wang J, Luo Z, Zhu K, Chen J and Shan H: Study of apparent diffusion coefficient value and histopathological differentiation of hepatocellular carcinoma. Zhonghua Yi Xue Za Zhi. 95:187–191. 2015.(In Chinese). PubMed/NCBI
22	Feng Y, Qin XC, Luo Y, Li YZ and Zhou X: Efficacy of contrast-enhanced ultrasound washout rate in predicting hepatocellular carcinoma differentiation. Ultrasound Med Biol. 41:1553–1560. 2015. View Article : Google Scholar : PubMed/NCBI
23	Ryborg AK, Johansen C, Iversen L and Kragballe K: Lysophosphatidylcholine induces keratinocyte differentiation and upregulation of AP-1- and NF-kappaB DNA-binding activity. Acta Derm Venereol. 84:433–438. 2004. View Article : Google Scholar : PubMed/NCBI
24	Zhou L, Ding L, Yin P, Lu X, Wang X, Niu J, Gao P and Xu G: Serum metabolic profiling study of hepatocellular carcinoma infected with hepatitis B or hepatitis C virus by using liquid chromatography-mass spectrometry. J Proteome Res. 11:5433–5442. 2012. View Article : Google Scholar : PubMed/NCBI
25	Mueller GP and Driscoll WJ: Biosynthesis of oleamide. Vitam Horm. 81:55–78. 2009. View Article : Google Scholar : PubMed/NCBI