Abstract
Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide. In the present study, we aimed to profile the possible changes in plasma phospholipid fatty acid composition of HCC patients, and to identify the fatty acid biomarkers that could distinguish HCC patients from healthy controls. A total of 37 plasma samples from healthy controls and HCC patients were collected and their phospholipid fatty acid profiles were characterized by gas chromatography–mass spectrometry followed by multivariate statistical analysis. Twenty-five fatty acids were identified and quantified, their proportions varied greatly between two groups, suggesting each group has its own fatty acid pattern. Orthogonal partial least squares discriminant analysis in terms of fatty acid profiles showed that HCC patients could be clearly distinguished from healthy controls. More importantly, linoleic acid (18:2n-6), oleic acid (18:1n-9), arachidonic acid (20:4n-6) and palmitic acid (16:0) were identified as the potential fatty acid biomarkers of HCC patients. Additionally, to further identify the major cause of the abnormality of plasma fatty acid profile, fatty acid distributions of cancerous tissue and its surrounding tissue from 42 HCC patients were also examined. Due to have similar variation trend of major fatty acid biomarkers, linoleic acid (18:2n-6), oleic acid (18:1n-9), abnormalities in plasma phospholipid fatty acid profiles of HCC patients may be mainly attributed to the alternation of intrinsic fatty acid metabolism caused by cancer per se, but not to the differences in dietary factors.
Similar content being viewed by others
Abbreviations
- ALA:
-
α-Linolenic acid
- EI:
-
Electron impact
- DPA:
-
Docosapentaenoic acid
- DHA:
-
Docosahexaenoic acid
- EPA:
-
Eicosapentaenoic acid
- FAME:
-
Fatty acid methyl ester(s)
- HCC:
-
Hepatocellular carcinoma
- HPTLC:
-
High performance thin-layer chromatography
- MUFA:
-
Monounsaturated fatty acid(s)
- OPLS-DA:
-
Orthogonal partial least squares discriminant analysis
- PCA:
-
Principal component analysis
- PUFA:
-
Polyunsaturated fatty acid(s)
- SFA:
-
Saturated fatty acid(s)
- S/N:
-
Signal-to-noise
- TIC:
-
Total ion chromatogram
- VIP:
-
Variable important for the projection
References
Kassahun WT, Fangmann J, Harms J, Hauss J, Bartels M (2006) Liver resection and transplantation in the management of hepatocellular carcinoma: a review. Exp Clin Transpl 4:549–558
Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55:74–108
Njei B, Rotman Y, Ditah I, Lim JK (2015) Emerging trends in hepatocellular carcinoma incidence and mortality. Hepatology 61:191–199
Bosetti C, Turati F, La Vecchia C (2014) Hepatocellular carcinoma epidemiology. Best Pract Res Clin Gastroenterol 28:753–770
Zhang J, Zhang L, Ye X, Chen L, Zhang L, Gao Y, Kang JX, Cai C (2013) Characteristics of fatty acid distribution is associated with colorectal cancer prognosis. Prostaglandins Leukot Essent Fat Acids 88:355–360
Chaudry A, McClinton S, Moffat LE, Wahle KW (1991) Essential fatty acid distribution in the plasma and tissue phospholipids of patients with benign and malignant prostatic disease. Br J Cancer 64:1157–1160
Macleod RI, Cassidy D, Laker MF, Soames JV (1990) Fatty acid composition of clinically healthy and malignant oral epithelium. J Oral Pathol Med 19:149–151
Gao M, Sun K, Guo M, Gao H, Liu K, Yang C, Li S, Liu N (2015) Fish consumption and n-3 polyunsaturated fatty acids, and risk of hepatocellular carcinoma: systematic review and meta-analysis. Cancer Causes Control 26:367–376
Wan JB, Huang LL, Rong R, Tan R, Wang J, Kang JX (2010) Endogenously decreasing tissue n-6/n-3 fatty acid ratio reduces atherosclerotic lesions in apolipoprotein E-deficient mice by inhibiting systemic and vascular inflammation. Arterioscler Thromb Vasc Biol 30:2487–2494
Tan B, Liang Y, Yi L, Li H, Zhou Z, Ji X, Deng J (2010) Identification of free fatty acids profiling of type 2 diabetes mellitus and exploring possible biomarkers by GC–MS coupled with chemometrics. Metabolomics 6:219–228
Zhao C, Mao J, Ai J, Shenwu M, Shi T, Zhang D, Wang X, Wang Y, Deng Y (2013) Integrated lipidomics and transcriptomic analysis of peripheral blood reveals significantly enriched pathways in type 2 diabetes mellitus. BMC Med Genom 6:S12
Zhang XJ, Huang LL, Su HX, Chen YX, Huang J, He CW, Li P, Yang DZ, Wan JB (2014) Characterizing plasma phospholipid fatty acid profiles of polycystic ovary syndrome patients with and without insulin resistance using GC–MS and chemometrics approach. J Pharm Biomed Anal 95:85–92
Wang DC, Sun CH, Liu LY, Sun XH, Jin XW, Song WL, Liu XQ, Wan XL (2012) Serum fatty acid profiles using GC–MS and multivariate statistical analysis: potential biomarkers of Alzheimer’s disease. Neurobiol Aging 33:1057–1066
Murphy RA, Bureyko TF, Mourtzakis M, Chu QS, Clandinin MT, Reiman T, Mazurak VC (2012) Aberrations in plasma phospholipid fatty acids in lung cancer patients. Lipids 47:363–369
Kobayakawa M, Yamawaki S, Hamazaki K, Akechi T, Inagaki M, Uchitomi Y (2005) Levels of omega-3 fatty acid in serum phospholipids and depression in patients with lung cancer. Br J Cancer 93:1329–1333
Tania M, Khan MA, Song Y (2010) Association of lipid metabolism with ovarian cancer. Curr Oncol 17:6–11
Cvetkovic Z, Vucic V, Cvetkovic B, Petrovic M, Ristic-Medic D, Tepsic J, Glibetic M (2010) Abnormal fatty acid distribution of the serum phospholipids of patients with non-Hodgkin lymphoma. Ann Hematol 89:775–782
Chajes V, Jenab M, Romieu I, Ferrari P, Dahm CC, Overvad K, Egeberg R, Tjonneland A, Clavel-Chapelon F, Boutron-Ruault MC, Engel P, Teucher B, Kaaks R, Floegel A, Boeing H, Trichopoulou A, Dilis V, Karapetyan T, Mattiello A, Tumino R, Grioni S, Palli D, Vineis P, Bueno-de-Mesquita HB, Numans ME, Peeters PHM, Lund E, Navarro C, Quiros JR, Sanchez-Cantalejo E, Gurrea AB, Dorronsoro M, Regner S, Sonestedt E, Wirfalt E, Khaw KT, Wareham N, Allen NE, Crowe FL, Rinaldi S, Slimani N, Carneiro F, Riboli E, Gonzalez CA (2011) Plasma phospholipid fatty acid concentrations and risk of gastric adenocarcinomas in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST). Am J Clin Nutr 94:1304–1313
Chow CK (2009) Fatty acid composition of plasma phospholipids and risk of prostate cancer. Am J Clin Nutr 89:1946–1947
Al-Tamer YY, Mahmood AA (2004) Lipid components and fatty acid composition of Iraqi subjects who smoke and consume dairy products. Nutr Metab Cardiovasc Dis 14:94–96
Zhang XJ, Huang LL, Cai XJ, Li P, Wang YT, Wan JB (2013) Fatty acid variability in three medicinal herbs of Panax species. Chem Cent J 7:12
Zhang XJ, Qiu JF, Guo LP, Wang Y, Li P, Yang FQ, Su HX, Wan JB (2013) Discrimination of multi-origin Chinese herbal medicines using gas chromatography–mass spectrometry-based fatty acid profiling. Molecules 18:15329–15343
Wan JB, Bai X, Cai XJ, Rao Y, Wang YS, Wang YT (2013) Chemical differentiation of Da-Cheng-Qi-Tang, a Chinese medicine formula, prepared by traditional and modern decoction methods using UPLC/Q-TOFMS-based metabolomics approach. J Pharm Biomed Anal 83:34–42
Gallagher P, Tweedle DE (1983) Taste threshold and acceptability of commercial diets in cancer patients. JPEN J Parenter Enter Nutr 7:361–363
Mooppan MM, Subramanyam D, Gupta NM, Talwar BL (1977) Cholesterol and phospholipid concentrations in gall bladder and hepatic bile in patients with cholelithiasis. Indian J Med Res 65:232–235
McClinton S, Moffat LE, Horrobin DF, Manku MS (1991) Abnormalities of essential fatty acid distribution in the plasma phospholipids of patients with bladder cancer. Br J Cancer 63:314–316
Currie E, Schulze A, Zechner R, Walther TC, Farese RV Jr (2013) Cellular fatty acid metabolism and cancer. Cell Metab 18:153–161
Hildebrandt LA, Spennetta T, Elson C, Shrago E (1995) Utilization and preferred metabolic pathway of ketone bodies for lipid synthesis by isolated rat hepatoma cells. Am J Physiol 269:C22–C27
Hanai T, Hashimoto T, Nishiwaki K, Ono M, Akamo Y, Tanaka M, Mizuno I, Yura J (1993) Comparison of prostanoids and their precursor fatty acids in human hepatocellular carcinoma and noncancerous reference tissues. J Surg Res 54:57–60
Engan T, Bjerve KS, Hoe AL, Krane J (1995) Characterization of plasma lipids in patients with malignant disease by 13C nuclear magnetic resonance spectroscopy and gas liquid chromatography. Blood 85:1323–1330
Baro L, Hermoso JC, Nunez MC, Jimenez-Rios JA, Gil A (1998) Abnormalities in plasma and red blood cell fatty acid profiles of patients with colorectal cancer. Br J Cancer 77:1978–1983
Lv W, Yang T (2012) Identification of possible biomarkers for breast cancer from free fatty acid profiles determined by GC–MS and multivariate statistical analysis. Clin Biochem 45:127–133
Kurtova AV, Xiao J, Mo Q, Pazhanisamy S, Krasnow R, Lerner SP, Chen F, Roh TT, Lay E, Ho PL, Chan KS (2015) Blocking PGE2-induced tumour repopulation abrogates bladder cancer chemoresistance. Nature 517:209–213
Goodwin JS, Ceuppens J (1983) Regulation of the immune response by prostaglandins. J Clin Immunol 3:295–315
Mayoral R, Fernandez-Martinez A, Bosca L, Martin-Sanz P (2005) Prostaglandin E2 promotes migration and adhesion in hepatocellular carcinoma cells. Carcinogenesis 26:753–761
Acknowledgments
This study was supported by grants from the Research Committee of the University of Macau (MYRG123-ICMS12 and MYRG111-ICMS13 to JB Wan) and from the Macao Science and Technology Development Fund (010/2013/A1 to JB Wan).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that there are no conflicts of interest.
About this article
Cite this article
Qiu, JF., Zhang, KL., Zhang, XJ. et al. Abnormalities in Plasma Phospholipid Fatty Acid Profiles of Patients with Hepatocellular Carcinoma. Lipids 50, 977–985 (2015). https://doi.org/10.1007/s11745-015-4060-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11745-015-4060-6