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

Fukutake N, Ueno M, Hiraoka N, Shimada K, Shiraishi K, Saruki N, Ito T, Yamakado M, Ono N, Imaizumi A, Kikuchi S, Yamamoto H, Katayama K - PLoS ONE (2015)

Bottom Line: Several amino acid concentrations in plasma were significantly altered in PC.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.These findings suggest that the PFAA profile of PC was significantly different from that of HC.

View Article: PubMed Central - PubMed

Affiliation: Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center of Cancer and Cardiovascular Diseases, Osaka, Japan.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

PFAA profiles of PC patients.The results of receiver–operator characteristic (ROC) curve analysis of PFAA profiles in the training set (120 PC and matching 600 HC). Axes show the AUC of ROC for each amino acid to discriminate patients from healthy controls. Black bold lines indicate the point where the AUC of ROC = 0.5.
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pone.0132223.g002: PFAA profiles of PC patients.The results of receiver–operator characteristic (ROC) curve analysis of PFAA profiles in the training set (120 PC and matching 600 HC). Axes show the AUC of ROC for each amino acid to discriminate patients from healthy controls. Black bold lines indicate the point where the AUC of ROC = 0.5.

Mentions: We first measured the concentrations of 19 plasma amino acids in the training set by HPLC–ESI–MS and found significant increases in Ser concentrations and significant decreases in the concentrations of 14 amino acids (Thr, Asn, Pro, Ala, Cit, Val, Met, Leu, Tyr, Phe, His, Trp, Lys and Arg) in PC patients compared with HC subjects (p < 0.05) (Table 2, S1 Fig). The PFAA profiles were subjected to AUC of ROC analysis because the levels of significance are dependent on the sample size (Fig 2, S1 Table). Plasma Ser concentrations were especially higher, while Trp and His concentrations were particularly lower in PC patients compared with HC subjects. The PFAA profiles of PC patients with stage 0–IIB disease, as a resectable stage subgroup, were almost similar to those of all other PC patients.


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

Fukutake N, Ueno M, Hiraoka N, Shimada K, Shiraishi K, Saruki N, Ito T, Yamakado M, Ono N, Imaizumi A, Kikuchi S, Yamamoto H, Katayama K - PLoS ONE (2015)

PFAA profiles of PC patients.The results of receiver–operator characteristic (ROC) curve analysis of PFAA profiles in the training set (120 PC and matching 600 HC). Axes show the AUC of ROC for each amino acid to discriminate patients from healthy controls. Black bold lines indicate the point where the AUC of ROC = 0.5.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4489861&req=5

pone.0132223.g002: PFAA profiles of PC patients.The results of receiver–operator characteristic (ROC) curve analysis of PFAA profiles in the training set (120 PC and matching 600 HC). Axes show the AUC of ROC for each amino acid to discriminate patients from healthy controls. Black bold lines indicate the point where the AUC of ROC = 0.5.
Mentions: We first measured the concentrations of 19 plasma amino acids in the training set by HPLC–ESI–MS and found significant increases in Ser concentrations and significant decreases in the concentrations of 14 amino acids (Thr, Asn, Pro, Ala, Cit, Val, Met, Leu, Tyr, Phe, His, Trp, Lys and Arg) in PC patients compared with HC subjects (p < 0.05) (Table 2, S1 Fig). The PFAA profiles were subjected to AUC of ROC analysis because the levels of significance are dependent on the sample size (Fig 2, S1 Table). Plasma Ser concentrations were especially higher, while Trp and His concentrations were particularly lower in PC patients compared with HC subjects. The PFAA profiles of PC patients with stage 0–IIB disease, as a resectable stage subgroup, were almost similar to those of all other PC patients.

Bottom Line: Several amino acid concentrations in plasma were significantly altered in PC.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.These findings suggest that the PFAA profile of PC was significantly different from that of HC.

View Article: PubMed Central - PubMed

Affiliation: Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center of Cancer and Cardiovascular Diseases, Osaka, Japan.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus