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PLoS One. 2015 Jul 2;10(7):e0132223. doi: 10.1371/journal.pone.0132223. eCollection 2015.

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

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Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center of Cancer and Cardiovascular Diseases, Osaka, Japan.
Division of Hepatobiliary and Pancreatic Medical Oncology, Kanagawa Cancer Center, Kanagawa, Japan.
Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan.
Hepatobiliary and Pancreatic Surgery Division, National Cancer Center Hospital, Tokyo, Japan.
Division of Gastroenterology, Department of Internal Medicine, Tokai University Oiso Hospital, Kanagawa, Japan.
Department of Anesthesia, Gunma Prefectural Cancer Center, Gunma, Japan.
Department of Gastroenterology and Hepatology, Japan Community Healthcare Organization (JCHO), Osaka Hospital, Osaka, Japan.
Center for Multiphasic Health Testing and Services, Mitsui Memorial Hospital, Tokyo, Japan.
Institute for Innovation, Ajinomoto Co., Inc., Kanagawa, Japan.



The incidence of pancreatic cancer (PC) continues to increase in the world, while most patients are diagnosed with advanced stages and survive <12 months. This poor prognosis is attributable to difficulty of early detection. Here we developed and evaluated a multivariate index composed of plasma free amino acids (PFAAs) for early detection of PC.


We 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).


Several 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.


These 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.

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