Abstract
To establish a screening strategy for pancreatic cancer (PC) based on new-onset diabetic mellitus (NO-DM), serum metabolomics analysis and a search for the metabolic pathways associated with PC related DM were performed. Serum samples from patients with NO-DM (n = 30) and patients with pancreatic cancer and NO-DM were examined by liquid chromatography-mass spectrometry. Data were analyzed using principal components analysis (PCA) and orthogonal projection to latent structures (OPLS) of the most significant metabolites. The diagnostic model was constructed using logistic regression analysis. Metabolic pathways were analyzed using the web-based tool MetPA. PC patients with NO-DM were older and had a lower BMI and shorter duration of DM than those with NO-DM. The metabolomic profiles of patients with PC and NO-DM were significantly different from those of patients with NO-DM in the PCA and OPLS models. Sixty two differential metabolites were identified by the OPLS model. The logistic regression model using a panel of two metabolites including N_Succinyl_L_diaminopimelic_acid and PE (18:2) had high sensitivity (93.3%) and specificity (93.1%) for PC. The top three metabolic pathways associated with PC related DM were valine, leucine and isoleucine biosynthesis and degradation, primary bile acid biosynthesis, and sphingolipid metabolism. In conclusion, screening for PC based on NO-DM using serum metabolomics in combination with clinic characteristics and CA19-9 is a potential useful strategy. Several metabolic pathways differed between PC related DM and type 2 DM.
Highlights
Pancreatic cancer (PC) is characterized by rapid tumor progression and early metastasis, and is one of the leading causes of cancer-related death
All patients in the pancreatic cancer (PC) group had pancreatic ductal adenocarcinoma (PDAC); samples were collected before surgery
Differential metabolites identified in a search of the database are listed in Supplementary Table 1 We used Random Forest (RF) to build a classification model based on these metabolites
Summary
Pancreatic cancer (PC) is characterized by rapid tumor progression and early metastasis, and is one of the leading causes of cancer-related death. The only curative treatment for pancreatic cancer is surgical resection, more than 80% of patients with pancreatic cancer have locally advanced or metastatic tumors that are unresectable at the time of diagnosis [1,2,3]. Because of the lack of effective early diagnostic methods, there is currently no standard protocol for screening patients at risk of pancreatic cancer (e.g., those with a family history of PC and chronic pancreatitis) [3, 4]. There is increasing evidence that diabetes mellitus (DM) is related to PC [4,5,6,7]. Our group and others proposed a NO-DM based screening strategy for PC [5, 8]
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