Metabolomic profile in pancreatic cancer patients: a consensus-based approach to identify highly discriminating metabolites

Abstract

Purposepancreatic adenocarcinoma is the fourth leading cause of cancer related deaths due to its aggressive behavior and poor clinical outcome. There is a considerable variability in the frequency of serum tumor markers in cancer' patients. We performed a metabolomics screening in patients diagnosed with pancreatic cancer.Experimental DesignTwo targeted metabolomic assays were conducted on 40 serum samples of patients diagnosed with pancreatic cancer and 40 healthy controls. Multivariate methods and classification trees were performed.Materials and MethodsSparse partial least squares discriminant analysis (SPLS-DA) was used to reduce the high dimensionality of a pancreatic cancer metabolomic dataset, differentiating between pancreatic cancer (PC) patients and healthy subjects. Using Random Forest analysis palmitic acid, 1,2-dioleoyl-sn-glycero-3-phospho-rac-glycerol, lanosterol, lignoceric acid, 1-monooleoyl-rac-glycerol, cholesterol 5α,6α epoxide, erucic acid and taurolithocholic acid (T-LCA), oleoyl-L-carnitine, oleanolic acid were identified among 206 metabolites as highly discriminating between disease states. Comparison between Receiver Operating Characteristic (ROC) curves for palmitic acid and CA 19-9 showed that the area under the ROC curve (AUC) of palmitic acid (AUC=1.000; 95% confidence interval) is significantly higher than CA 19-9 (AUC=0.963; 95% confidence interval: 0.896-1.000).ConclusionMass spectrometry-based metabolomic profiling of sera from pancreatic cancer patients and normal subjects showed significant alterations in the profiles of the metabolome of PC patients as compared to controls. These findings offer an information-rich matrix for discovering novel candidate biomarkers with diagnostic or prognostic potentials.

White Adipose Tissue Browning: A Double-edged Sword

“…Lipodomic profiling in burn and cancer patients has revealed increased saturated FFAs (e.g., palmitate) linked to pro-inflammation and metabolic dysfunction [41] [42] [29]. In contrast, the expression profiles of good lipids such as polyunsaturated FAs (PUFAs) that have been shown to attenuate inflammation are significantly depleted in these hypermetabolic patients [43] [29].…”

“…In fact, proteins are covalently modified with a great variety of lipids: most frequently palmitate and myristate, abundant FFAs in hypermetabolic patients [29] [41]. Traditionally, protein palmitoylation has been thought to only mediate protein trafficking and stability [73].…”

Racial disparity in metabolic regulation of cancer

“…Blood plasma or serum has been extensively used in different cancer types, such as breast, colorectal, pancreatic, and lung cancers to delineate metabolic markers (155, 156). Metabolic profiling of sera from pancreatic cancer patients and healthy subjects showed alterations in levels of 206 metabolites capable of discriminating disease states (157, 158). Further, metabolomic analysis of the pancreatic cancer patient's serum from Japanese and Caucasian populations demonstrated lower levels of serum phospholipids and ultra-long-chain fatty acid, PC-594 (159).…”

Host-Microbiome Interaction and Cancer: Potential Application in Precision Medicine

“…Metabolomic studies have led us to search for new biomarkers in cancer, and these findings have had important implications for surveying the mechanisms of a variety of cancers such as bladder (Rodrigues et al, 2016), breast (Jobard et al, 2014), pancreatic (Di Gangi et al, 2015), gastroesophageal (Abbassi-Ghadi et al, 2013), gastric (Abbassi-Ghadi et al, 2013; Chan et al, 2016), and oral (Mikkonen et al, 2015) cancer. For instance, in the case of gastric cancer, three potential biomarkers, 2-hydroxyisobutyrate, 3-indoxylsulfate and alanine, were identified in urine samples using 1 H-NMR spectroscopy.…”