4.3 Article

Serum metabolomics differentiating pancreatic cancer from new-onset diabetes

Journal

ONCOTARGET
Volume 8, Issue 17, Pages 29116-29124

Publisher

IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.16249

Keywords

pancreatic cancer; metabolomics; serum; new-onset diabetes

Funding

  1. National Nature Science Foundation of China [81302087]
  2. Municipal Natural Science Foundation of Shanghai of China [13ZR1457400]
  3. Specialized Research Fund for the Doctoral Program of Higher Education [20130073120004]

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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.

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