A Novel Serum Metabolomic Profile for the Differential Diagnosis of Distal Cholangiocarcinoma and Pancreatic Ductal Adenocarcinoma

Abstract

The diagnosis of adenocarcinomas located in the pancreas head, i.e., distal cholangiocarcinoma (dCCA) and pancreatic ductal adenocarcinoma (PDAC), constitutes a clinical challenge because they share many symptoms, are not easily distinguishable using imaging techniques and accurate biomarkers are not available. Searching for biomarkers with potential usefulness in the differential diagnosis of these tumors, we have determined serum metabolomic profiles in healthy controls and patients with dCCA, PDAC or benign pancreatic diseases (BPD). Ultra-high-performance liquid chromatography coupled to mass spectrometry (UHPLC-MS) analysis was performed in serum samples from dCCA (n = 34), PDAC (n = 38), BPD (n = 42) and control (n = 25) individuals, divided into discovery and validation cohorts. This approach permitted 484 metabolites to be determined, mainly lipids and amino acids. The analysis of the results led to the proposal of a logistic regression model able to discriminate patients with dCCA and PDAC (AUC value of 0.888) based on the combination of serum levels of nine metabolites (acylcarnitine AC(16:0), ceramide Cer(d18:1/24:0), phosphatidylcholines PC(20:0/0:0) and PC(O-16:0/20:3), lysophosphatidylcholines PC(20:0/0:0) and PC(0:0/20:0), lysophosphatidylethanolamine PE(P-18:2/0:0), and sphingomyelins SM(d18:2/22:0) and SM(d18:2/23:0)) and CA 19-9. In conclusion, we propose a novel specific panel of serum metabolites that can help in the differential diagnosis of dCCA and PDAC. Further validation of their clinical usefulness in prospective studies is required.

Identification of Circulating Endocan-1 and Ether Phospholipids as Biomarkers for Complications in Thalassemia Patients

“…However, we found ether PCs and PEs containing acyl chains in sn1 with 20 and 24 carbons, which were saturated or mono-unsaturated, for which much less is known about their biological role. These species were reported in two other patient populations, namely patients with non-alcoholic fatty liver disease [47] and with pancreatic cancer [48]. Their lower level in thalassemia patients could therefore be linked to pathological mechanisms, namely high oxidative stress or inflammatory status [49,50], and/or reflect a prevailing mitochondrial/peroxisomal dysfunction in one or more organs.…”

The Synergistic Effect of an ATP-Competitive Inhibitor of mTOR and Metformin on Pancreatic Tumor Growth

“…Taken together, our data obtained in an orthotopic pancreatic cancer mouse model indicate that mTOR inhibition has a favorable impact on pancreatic cancer outcome, evidenced by decreased pancreatic tumor weight (62% reduction in TLML compared with control) and tumor volume (49% reduction in TLML compared with control) ( Figure 1 ) and the associated changes in glucose and energy metabolism ( Figure 4 ). In humans, researchers conducted an untargeted metabolomics analysis in serum from patients and found 9 metabolites that might differentiate between PDAC and control ( 49 , 50 ), including ceramide and phospholipids. Other investigators employed an NMR approach to identify a metabolite signature of pancreatic cancer ( 51 ).…”

The Impact of Biomarkers in Pancreatic Ductal Adenocarcinoma on Diagnosis, Surveillance and Therapy

“…To discriminate PDAC from distal cholangiocarcinoma can be challenging. A nine-metabolite biomarker panel, consisting of mainly lipids, amino acids and CA19-9 allowed to distinguish PDAC ( n = 38) form distal cholangiocarcinoma patients ( n = 34), with a AUC of 0.888 [ 57 ].…”