Detection of Lung Cancer through Metabolic Changes Measured in Blood Plasma

被引:60
作者
Louis, Evelyne [1 ]
Adriaensens, Peter [2 ,3 ]
Guedens, Wanda [2 ]
Bigirumurame, Theophile [4 ]
Baeten, Kurt [5 ]
Vanhove, Karolien [1 ,6 ]
Vandeurzen, Kurt [7 ]
Darquennes, Karen [8 ]
Vansteenkiste, Johan [9 ]
Dooms, Christophe [9 ]
Shkedy, Ziv [4 ]
Mesotten, Liesbet [1 ,10 ]
Thomeer, Michiel [1 ,11 ]
机构
[1] Hasselt Univ, Fac Med & Life Sci, Hasselt, Belgium
[2] Hasselt Univ, Inst Mat Res, Biomol Design Grp, Hasselt, Belgium
[3] Hasselt Univ, Inst Mat Res, Appl & Analyt Chem, Hasselt, Belgium
[4] Hasselt Univ, Interuniv Inst Biostat & Stat Bioinformat, Hasselt, Belgium
[5] Janssen Diagnost BVBA, Beerse, Belgium
[6] Algemeen Ziekenhuis Vesalius, Dept Resp Med, Tongeren, Belgium
[7] Mariaziekenhuis Noord Limburg, Dept Resp Med, Overpelt, Belgium
[8] Ziekenhuis Maas Kempen, Dept Resp Med, Maaseik, Belgium
[9] Katholieke Univ Leuven, Univ Ziekenhuizen, Dept Resp Med, Leuven, Belgium
[10] Ziekenhuis Oost Limburg, Dept Nucl Med, Genk, Belgium
[11] Ziekenhuis Oost Limburg, Dept Resp Med, Schiepse Bos 6, B-3600 Genk, Belgium
关键词
Lung cancer; H-1-NMR spectroscopy; Metabolic phenotype; Blood plasma biomarker; Risk model; SPECTROSCOPY; METABONOMICS; SIGNATURES; MORTALITY; H-1-NMR; TUMORS;
D O I
10.1016/j.jtho.2016.01.011
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Introduction: Low-dose computed tomography, the currently used tool for lung cancer screening, is characterized by a high rate of false-positive results. Accumulating evidence has shown that cancer cell metabolism differs from that of normal cells. Therefore, this study aims to evaluate whether the metabolic phenotype of blood plasma allows detection of lung cancer. Methods: The proton nuclear magnetic resonance spectrum of plasma is divided into 110 integration regions, representing the metabolic phenotype. These integration regions reflect the relative metabolite concentrations and were used to train a classification model in discriminating between 233 patients with lung cancer and 226 controls. The validity of the model was examined by classifying an independent cohort of 98 patients with lung cancer and 89 controls. Results: The model makes it, possible to correctly classify 78% of patients with lung cancer and 92% of controls, with an area under the curve of 0.88. Important moreover is the fact that the model is convincing, which is demonstrated by validation in the independent cohort with a sensitivity of 71%, a specificity of 81%, and an area under the curve of 0.84. Patients with lung cancer have increased glucose and decreased lactate and phospholipid levels. The limited number of patients in the subgroups and their heterogeneous nature do not (yet) enable differentiation between histological subtypes and tumor stages. Conclusions: Metabolic phenotyping of plasma allows detection of lung cancer, even in an early stage. Increased glucose and decreased lactate levels are pointing to an increased gluconeogenesis and are in accordance with recently published findings. Furthermore, decreased phospholipid levels confirm the enhanced membrane synthesis. (C) 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
引用
收藏
页码:516 / 523
页数:8
相关论文
共 29 条
  • [21] Phenotyping human blood plasma by 1H-NMR: a robust protocol based on metabolite spiking and its evaluation in breast cancer
    Louis, Evelyne
    Bervoets, Liene
    Reekmans, Gunter
    De Jonge, Eric
    Mesotten, Liesbet
    Thomeer, Michiel
    Adriaensens, Peter
    [J]. METABOLOMICS, 2015, 11 (01) : 225 - 236
  • [22] The role of metabolites and metabolomics in clinically applicable biomarkers of disease
    Mamas, Mamas
    Dunn, Warwick B.
    Neyses, Ludwig
    Goodacre, Royston
    [J]. ARCHIVES OF TOXICOLOGY, 2011, 85 (01) : 5 - 17
  • [23] Lung cancer screening
    Mulshine, JL
    Sullivan, DC
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2005, 352 (26) : 2714 - 2720
  • [24] Cancer metabolism: current perspectives and future directions
    Munoz-Pinedo, C.
    El Mjiyad, N.
    Ricci, J-E
    [J]. CELL DEATH & DISEASE, 2012, 3 : e248 - e248
  • [25] Metabolic Signatures of Lung Cancer in Biofluids: NMR-Based Metabonomics of Blood Plasma
    Rocha, Claudia M.
    Carrola, Joana
    Barros, Antonio S.
    Gil, Ana M.
    Goodfellow, Brian J.
    Carreira, Isabel M.
    Bernardo, Joao
    Gomes, Ana
    Sousa, Vitor
    Carvalho, Lina
    Duarte, Iola F.
    [J]. JOURNAL OF PROTEOME RESEARCH, 2011, 10 (09) : 4314 - 4324
  • [26] Lipid metabolism in cancer
    Santos, Claudio R.
    Schulze, Almut
    [J]. FEBS JOURNAL, 2012, 279 (15) : 2610 - 2623
  • [27] The Metabolic Alterations of Cancer Cells
    Sciacovelli, Marco
    Gaude, Edoardo
    Hilvo, Mika
    Frezza, Christian
    [J]. CONCEPTUAL BACKGROUND AND BIOENERGETIC/MITOCHONDRIAL ASPECTS OF ONCOMETABOLISM, 2014, 542 : 1 - 23
  • [28] The Warburg effect: Insights from the past decade
    Upadhyay, Mohita
    Samal, Jasmine
    Kandpal, Manish
    Singh, Om Vir
    Vivekanandan, Perumal
    [J]. PHARMACOLOGY & THERAPEUTICS, 2013, 137 (03) : 318 - 330
  • [29] Exploratory investigation of plasma metabolomics in human lung adenocarcinoma
    Wen, Tao
    Gao, Liang
    Wen, Zongmei
    Wu, Chunyan
    Tan, Chuen Seng
    Toh, Wei Zhong
    Ong, Choon Nam
    [J]. MOLECULAR BIOSYSTEMS, 2013, 9 (09) : 2370 - 2378