Plasma metabolite biomarkers for the detection of pancreatic cancer

Guoxiang Xie, Lingeng Lu, Yunping Qiu, Quanxing Ni, Wei Zhang, Yu Tang Gao, Harvey A. Risch, Herbert Yu, Wei Jia

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Patients with pancreatic cancer (PC) are usually diagnosed at late stages, when the disease is nearly incurable. Sensitive and specific markers are critical for supporting diagnostic and therapeutic strategies. The aim of this study was to use a metabonomics approach to identify potential plasma biomarkers that can be further developed for early detection of PC. In this study, plasma metabolites of newly diagnosed PC patients (n = 100) and age- and gender-matched controls (n = 100) from Connecticut (CT), USA, and the same number of cases and controls from Shanghai (SH), China, were profiled using combined gas and liquid chromatography mass spectrometry. The metabolites consistently expressed in both CT and SH samples were used to identify potential markers, and the diagnostic performance of the candidate markers was tested in two sample sets. A diagnostic model was constructed using a panel of five metabolites including glutamate, choline, 1,5-anhydro-d-glucitol, betaine, and methylguanidine, which robustly distinguished PC patients in CT from controls with high sensitivity (97.7%) and specificity (83.1%) (area under the receiver operating characteristic curve [AUC] = 0.943, 95% confidence interval [CI] = 0.908-0.977). This panel of metabolites was then tested with the SH data set, yielding satisfactory accuracy (AUC = 0.835; 95% CI = 0.777-0.893), with a sensitivity of 77.4% and specificity of 75.8%. This model achieved a sensitivity of 84.8% in the PC patients at stages 0, 1, and 2 in CT and 77.4% in the PC patients at stages 1 and 2 in SH. Plasma metabolic signatures show promise as biomarkers for early detection of PC.

Original languageEnglish (US)
Pages (from-to)1195-1202
Number of pages8
JournalJournal of Proteome Research
Volume14
Issue number2
DOIs
StatePublished - Feb 6 2015

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Biomarkers
Metabolites
Pancreatic Neoplasms
Plasmas
Methylguanidine
Betaine
Sorbitol
Early Detection of Cancer
Liquid chromatography
Area Under Curve
Choline
Gas chromatography
Mass spectrometry
Glutamic Acid
Confidence Intervals
Sensitivity and Specificity
Metabolomics
ROC Curve
Gas Chromatography-Mass Spectrometry
China

Keywords

  • GC-MS
  • LC-MS
  • logistic regression
  • metabonomics
  • multivariate statistical analysis
  • OPLS-DA
  • Pancreatic cancer
  • plasma
  • ROC

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

Cite this

Plasma metabolite biomarkers for the detection of pancreatic cancer. / Xie, Guoxiang; Lu, Lingeng; Qiu, Yunping; Ni, Quanxing; Zhang, Wei; Gao, Yu Tang; Risch, Harvey A.; Yu, Herbert; Jia, Wei.

In: Journal of Proteome Research, Vol. 14, No. 2, 06.02.2015, p. 1195-1202.

Research output: Contribution to journalArticle

Xie, G, Lu, L, Qiu, Y, Ni, Q, Zhang, W, Gao, YT, Risch, HA, Yu, H & Jia, W 2015, 'Plasma metabolite biomarkers for the detection of pancreatic cancer', Journal of Proteome Research, vol. 14, no. 2, pp. 1195-1202. https://doi.org/10.1021/pr501135f
Xie, Guoxiang ; Lu, Lingeng ; Qiu, Yunping ; Ni, Quanxing ; Zhang, Wei ; Gao, Yu Tang ; Risch, Harvey A. ; Yu, Herbert ; Jia, Wei. / Plasma metabolite biomarkers for the detection of pancreatic cancer. In: Journal of Proteome Research. 2015 ; Vol. 14, No. 2. pp. 1195-1202.
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abstract = "Patients with pancreatic cancer (PC) are usually diagnosed at late stages, when the disease is nearly incurable. Sensitive and specific markers are critical for supporting diagnostic and therapeutic strategies. The aim of this study was to use a metabonomics approach to identify potential plasma biomarkers that can be further developed for early detection of PC. In this study, plasma metabolites of newly diagnosed PC patients (n = 100) and age- and gender-matched controls (n = 100) from Connecticut (CT), USA, and the same number of cases and controls from Shanghai (SH), China, were profiled using combined gas and liquid chromatography mass spectrometry. The metabolites consistently expressed in both CT and SH samples were used to identify potential markers, and the diagnostic performance of the candidate markers was tested in two sample sets. A diagnostic model was constructed using a panel of five metabolites including glutamate, choline, 1,5-anhydro-d-glucitol, betaine, and methylguanidine, which robustly distinguished PC patients in CT from controls with high sensitivity (97.7{\%}) and specificity (83.1{\%}) (area under the receiver operating characteristic curve [AUC] = 0.943, 95{\%} confidence interval [CI] = 0.908-0.977). This panel of metabolites was then tested with the SH data set, yielding satisfactory accuracy (AUC = 0.835; 95{\%} CI = 0.777-0.893), with a sensitivity of 77.4{\%} and specificity of 75.8{\%}. This model achieved a sensitivity of 84.8{\%} in the PC patients at stages 0, 1, and 2 in CT and 77.4{\%} in the PC patients at stages 1 and 2 in SH. Plasma metabolic signatures show promise as biomarkers for early detection of PC.",
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