Plasma Fatty Acid Composition in Patients with Pancreatic Cancer: Correlations to Clinical Parameters
Plasma Fatty Acid Composition in Patients with Pancreatic Cancer: Correlations to Clinical Parameters
Year: 2012
Authors: Macasek, J. Vecka, M. Zak, A. Urbanek, M. Krechler, T.
Publication Name: Nutrition & Cancer
Publication Details: Volume 64; Issue 7; Pages 946-955
Abstract:
Pancreatic cancer (PC) ranks as the fourth cause of cancer related deaths in the Czech Republic. Evidence exists that deregulation of fatty acid (FA) metabolism is connected with some malignancies; therefore, we decided to analyze FA profile in plasma lipid classes in patients with PC with relation to tumor staging, nutritional status, and survival. The study included 84 patients (47 males, 37 females) with PC and 68 controls (36 males, 32 females). FA patterns were analyzed in plasma lipid classes by gas chromatography. We observed increased proportion of total monounsaturated FA (MUFA) in PC group in all plasma lipid classes. These changes were connected with increased delta 9 desaturase (SCD1) and delta 5 desaturase indices. Correlations of dihomo gamma linolenic acid (DHGLA) with these variables were opposite. Longer survival of patients was connected with higher content of EPA, DHA, and with lower SCD1 index, respectively. Plasma phospholipid proportions of alpha linolenic acid, DHGLA, EPA, and n3 polyunsaturated fatty acids displayed negative trend with tumor staging. Plasma lipid FA pattern in PC patients resulted from decreased dietary fat intake and increased de novo synthesis of FA with transformation into MUFA. Changes in FA profile implicated some pathophysiological mechanisms responsible for disturbed FA metabolism in PC and importance of appropriate nutritional support. (Authors abstract)
Pancreatic cancer (PC) is one of the most fatal human malignancies. It ranks as the fourth cause of cancer-related deaths in the United States as well as in the Czech Republic. There is growing evidence that the deregulation of fatty acid (FA) metabolism is connected with some malignancies similar to cardiovascular disease, metabolic and nutritional disease (such as obesity, diabetes mellitus, and other insulin resistance states). FA composition in plasma phospholipids (PL) and cholesteryl esters (CE) reflects both dietary intake of FA over a 6 week to 3 month period as well as endogenous FA metabolism (synthesis of FA de novo, beta oxidation, enzymatic desaturation and elongation, conversion of polyunsaturated FA to eicosanoids, and lipoperoxidation. The de novo biosynthesis of FA is induced in several types of malignant tumors by overexpression of FA synthase (FAS) and stearoyl-CoA desaturase (SCD1). High intake of n6 PUFA, especially linoleic acid (LA; 18:2n6), and the elevated ratio of n6 PUFA to n3 PUFA also increased the risk for alimentary tract tumors (colorectal carcinoma, pancreas) and breast and prostate cancer. Beneficial effects of n3 PUFA (ratio n6 PUFA to n3 PUFA, respectively) in the risk and progression of several carcinoma were reported in epidemiological studies. n6 PUFA enhances tumor growth by supporting tumor proliferation, invasiveness, metastases formation, and apoptosis as well as the reaction of the organism (inflammation, immune responses, and angiogenesis) whereas n3 PUFA opposes these effects.
The aim of the study was to analyze the profile of FA in the main plasma lipid classes: PL, CE, and triacylglycerols (TAG) in relation to tumor staging, nutritional status, and survival in the patients with PC. Decreased levels of LA, ALA, and EPA were found in the PC group. Patients with PC did not exhibit increased concentrations of conjugated dienes in LDL particles, a marker of lipoperoxidation. The observed decreased proportions of LA, ALA, and EPA are not caused by the systemic oxidative stress or lipoperoxidation but more likely by lowered dietary intake of these FA. The decreased LA, ALA, and EPA content can be also induced by malabsorption which is highly probable in PC. Increased activity of SCD1 is usually observed in various cancers. Aggressively growing tumors are characterized by an elevated synthesis of FA de novo and accelerated transformation of SFA to MFA, which is combined with synthetic (FAS) and desaturation (SCD1) activities. FAS is a multifunctional enzymatic complex that synthesizes palmitic acid (C16:0) from acetyl-CoA and malonyl-CoA. FAS as well as SCD1 has elevated activities in cancer cells, where the de novo synthesis is important for cell membrane synthesis, membrane remodeling, and proliferation. In states with an absolute and relative lack of PUFA (n6 or n3), SCD1 is necessary for maintenance of cellular lipid homeostasis, because it keeps the synthesis of MUFA that is essential for complex lipid formation. In this study, trends for a decreased content of PUFA n3, ALA, EPA, and DHGLA with an increased burden of disease were observed. In the PC group, higher SCD1 and D5D indices as well as both desaturation activity indices of palmitate (16:1 to 16:0) and stearate (18:1n-9 to 18:0) were noted. In conclusion, a specific plasma esters FA profile in patients with PC was described. In comparison with control subjects, patients with PC revealed increased concentrations of monounsaturated FA. These changes were associated with increased index of SCD1. Decreased concentrations of LA, ALA, and EPA were found in plasma lipid esters of PC patients, and these changes are probably caused by a lower intake of dietary fat. Positive correlations between levels of visceral proteins and concentrations of EPA and DHGLA were found. These FA negatively correlated with concentration of CRP. Index of SCD-1 in PL correlated negatively with survival time of the patients. Longer survival of the patients was connected with higher content of EPA, DHA, and with lower index of SCD-1 activity, respectively. Proportions of PUFA n3 displayed a negative trend with tumor staging, whereas the positive trends of MUFA, SCD1, and on the degree of malnutrition as well as the negative trend of DHGLA content to the extent of malnutrition were found. The changes in FA profile implicate pathophysiological mechanisms responsible for disturbed FA metabolism in cancer patients and indicate the importance of appropriate nutritional support. (Editors comments)
