Metabonomic models of human pancreatic cancer using 1D proton NMR spectra of lipids in plasma

被引:71
作者
Beger, Richard D. [1 ]
Schnackenberg, Laura K.
Holland, Ricky D.
Li, Donghui
Dragan, Yvonne
机构
[1] Natl Ctr Toxicol Res, Div Syst Toxicol Food & Drug Adm, Jefferson, AR 72079 USA
[2] Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA
基金
美国国家卫生研究院;
关键词
metabonomics; metabolomics; lipiclomics; NMR; pancreatic cancer;
D O I
10.1007/s11306-006-0026-2
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
In this study, we hypothesized that the altered insulin and glucose levels in male pancreatic cancer patients reported in a recent JAMA article would result in an altered lipid profile in the blood of pancreatic cancer patients when compared to controls (Stolzenberg-Solomon et al., 2005). Proton nuclear magnetic resonance (NMR) spectra of human lipophilic plasma extracts were used in order to build partial least squares discriminant function (PLS-DF) models that classified samples as belonging to the pancreatic control group or to the pancreatic cancer group. The sensitivity, specificity, and overall accuracy of the PLS-DF models based on 4 bins were 96%, 88%, and 92%, respectively. The sensitivity, specificity, and overall accuracy of the PLS-DF models based on 5 bins were 98%, 94%, and 96%, respectively. The sensitivity, specificity and overall accuracy of both the 4-bin and 5-bin PLS-DF models dropped only 1-2% during leave-25%-out cross-validation testing. Mass spectrometric profiling of phospholipids in plasma found three phosphatidylinositols that were significantly lower in pancreatic cancer patients than in healthy controls. The cancer models are based upon changes in lipid profiles that may provide a more sensitive and accurate diagnosis of pancreatic cancer than current methods that are based upon a single biomarker.
引用
收藏
页码:125 / 134
页数:10
相关论文
共 47 条
[1]   Serum antioxidant and cholesterol levels in patients with different types of cancer [J].
Abiaka, C ;
Al-Awadi, F ;
Al-Sayer, H ;
Gulshan, S ;
Behbehani, A ;
Farghally, M ;
Simbeye, A .
JOURNAL OF CLINICAL LABORATORY ANALYSIS, 2001, 15 (06) :324-330
[2]  
BASSO D, 1990, ITAL J GASTROENTEROL, V22, P1
[3]   Discriminant function analyses of liver-specific carcinogens [J].
Beger, RD ;
Young, JF ;
Fang, H .
JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES, 2004, 44 (03) :1107-1110
[4]  
BLIGH EG, 1959, CAN J BIOCHEM PHYS, V37, P911
[5]  
Brindle JT, 2002, NAT MED, V8, P1439, DOI 10.1038/nm802
[6]   Quantitative analysis of biological membrane lipids at the low picomole level by nano-electrospray ionization tandem mass spectrometry [J].
Brugger, B ;
Erben, G ;
Sandhoff, R ;
Wieland, FT ;
Lehmann, WD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (06) :2339-2344
[7]   The value of biliary amylase and Hepatocarcinoma-Intestine-Pancreas Pancreatitis-associated Protein I (HIP/PAP-1) in diagnosing biliary malignancies [J].
Chen, CY ;
Lin, XZ ;
Wu, HC ;
Shiesh, SC .
CLINICAL BIOCHEMISTRY, 2005, 38 (06) :520-525
[8]  
CHUMURNY GN, 1988, NMR BIOMED, V1, P136
[9]   CROSS-VALIDATION, BOOTSTRAPPING, AND PARTIAL LEAST-SQUARES COMPARED WITH MULTIPLE-REGRESSION IN CONVENTIONAL QSAR STUDIES [J].
CRAMER, RD ;
BUNCE, JD ;
PATTERSON, DE ;
FRANK, IE .
QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS, 1988, 7 (01) :18-25
[10]  
Cwik Grzegorz, 2004, Ann Univ Mariae Curie Sklodowska Med, V59, P213