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

BACKGROUND: 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 compose...

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Autores principales: Fukutake, Nobuyasu, Ueno, Makoto, Hiraoka, Nobuyoshi, Shimada, Kazuaki, Shiraishi, Koichi, Saruki, Nobuhiro, Ito, Toshifumi, Yamakado, Minoru, Ono, Nobukazu, Imaizumi, Akira, Kikuchi, Shinya, Yamamoto, Hiroshi, Katayama, Kazuhiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4489861/
https://www.ncbi.nlm.nih.gov/pubmed/26133769
http://dx.doi.org/10.1371/journal.pone.0132223
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author Fukutake, Nobuyasu
Ueno, Makoto
Hiraoka, Nobuyoshi
Shimada, Kazuaki
Shiraishi, Koichi
Saruki, Nobuhiro
Ito, Toshifumi
Yamakado, Minoru
Ono, Nobukazu
Imaizumi, Akira
Kikuchi, Shinya
Yamamoto, Hiroshi
Katayama, Kazuhiro
author_facet Fukutake, Nobuyasu
Ueno, Makoto
Hiraoka, Nobuyoshi
Shimada, Kazuaki
Shiraishi, Koichi
Saruki, Nobuhiro
Ito, Toshifumi
Yamakado, Minoru
Ono, Nobukazu
Imaizumi, Akira
Kikuchi, Shinya
Yamamoto, Hiroshi
Katayama, Kazuhiro
author_sort Fukutake, Nobuyasu
collection PubMed
description BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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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spelling pubmed-44898612015-07-15 A Novel Multivariate Index for Pancreatic Cancer Detection Based On the Plasma Free Amino Acid Profile Fukutake, Nobuyasu Ueno, Makoto Hiraoka, Nobuyoshi Shimada, Kazuaki Shiraishi, Koichi Saruki, Nobuhiro Ito, Toshifumi Yamakado, Minoru Ono, Nobukazu Imaizumi, Akira Kikuchi, Shinya Yamamoto, Hiroshi Katayama, Kazuhiro PLoS One Research Article BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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. Public Library of Science 2015-07-02 /pmc/articles/PMC4489861/ /pubmed/26133769 http://dx.doi.org/10.1371/journal.pone.0132223 Text en © 2015 Fukutake et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Fukutake, Nobuyasu
Ueno, Makoto
Hiraoka, Nobuyoshi
Shimada, Kazuaki
Shiraishi, Koichi
Saruki, Nobuhiro
Ito, Toshifumi
Yamakado, Minoru
Ono, Nobukazu
Imaizumi, Akira
Kikuchi, Shinya
Yamamoto, Hiroshi
Katayama, Kazuhiro
A Novel Multivariate Index for Pancreatic Cancer Detection Based On the Plasma Free Amino Acid Profile
title A Novel Multivariate Index for Pancreatic Cancer Detection Based On the Plasma Free Amino Acid Profile
title_full A Novel Multivariate Index for Pancreatic Cancer Detection Based On the Plasma Free Amino Acid Profile
title_fullStr A Novel Multivariate Index for Pancreatic Cancer Detection Based On the Plasma Free Amino Acid Profile
title_full_unstemmed A Novel Multivariate Index for Pancreatic Cancer Detection Based On the Plasma Free Amino Acid Profile
title_short A Novel Multivariate Index for Pancreatic Cancer Detection Based On the Plasma Free Amino Acid Profile
title_sort novel multivariate index for pancreatic cancer detection based on the plasma free amino acid profile
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4489861/
https://www.ncbi.nlm.nih.gov/pubmed/26133769
http://dx.doi.org/10.1371/journal.pone.0132223
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