PLoS ONE (Jan 2015)

A Novel Multivariate Index for Pancreatic Cancer Detection Based On the Plasma Free Amino Acid Profile.

  • Nobuyasu Fukutake,
  • Makoto Ueno,
  • Nobuyoshi Hiraoka,
  • Kazuaki Shimada,
  • Koichi Shiraishi,
  • Nobuhiro Saruki,
  • Toshifumi Ito,
  • Minoru Yamakado,
  • Nobukazu Ono,
  • Akira Imaizumi,
  • Shinya Kikuchi,
  • Hiroshi Yamamoto,
  • Kazuhiro Katayama

DOI
https://doi.org/10.1371/journal.pone.0132223
Journal volume & issue
Vol. 10, no. 7
p. e0132223

Abstract

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BackgroundThe incidence of pancreatic cancer (PC) continues to increase in the world, while most patients are diagnosed with advanced stages and survive MethodsWe conducted a cross-sectional study in multi-institutions in Japan. Fasting plasma samples from PC patients (n = 360), chronic pancreatitis (CP) patients (n = 28), and healthy control (HC) subjects (n = 8372) without apparent cancers who were undergoing comprehensive medical examinations were collected. Concentrations of 19 PFAAs were measured by liquid chromatography-mass spectrometry. We generated an index consisting of the following six PFAAs: serine, asparagine, isoleucine, alanine, histidine, and tryptophan as variables for discrimination in a training set (120 PC and matching 600 HC) and evaluation in a validation set (240 PC, 28 CP, and 7772 HC).ResultsSeveral amino acid concentrations in plasma were significantly altered in PC. Plasma tryptophan and histidine concentrations in PC were particularly low, while serine was particularly higher than that of HC. The area under curve (AUC) based on receiver operating characteristic (ROC) curve analysis of the resulting index to discriminate PC from HC were 0.89 [95% confidence interval (CI), 0.86-0.93] in the training set. In the validation set, AUCs based on ROC curve analysis of the PFAA index were 0.86 (95% CI, 0.84-0.89) for all PC patients versus HC subjects, 0.81 (95% CI, 0.75-0.86) for PC patients from stage IIA to IIB versus HC subjects, and 0.87 (95% CI, 0.80-0.93) for all PC patients versus CP patients.ConclusionsThese findings suggest that the PFAA profile of PC was significantly different from that of HC. The PFAA index is a promising biomarker for screening and diagnosis of PC.