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
  • [1] Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening
    Aberle, Denise R.
    Adams, Amanda M.
    Berg, Christine D.
    Black, William C.
    Clapp, Jonathan D.
    Fagerstrom, Richard M.
    Gareen, Ilana F.
    Gatsonis, Constantine
    Marcus, Pamela M.
    Sicks, JoRean D.
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2011, 365 (05) : 395 - 409
  • [2] Benefits and Harms of CT Screening for Lung Cancer A Systematic Review
    Bach, Peter B.
    Mirkin, Joshua N.
    Oliver, Thomas K.
    Azzoli, Christopher G.
    Berry, Donald A.
    Brawley, Otis W.
    Byers, Tim
    Colditz, Graham A.
    Gould, Michael K.
    Jett, James R.
    Sabichi, Anita L.
    Smith-Bindman, Rebecca
    Wood, Douglas E.
    Qaseem, Amir
    Detterbeck, Frank C.
    [J]. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2012, 307 (22): : 2418 - 2429
  • [3] Hooked on fat: the role of lipid synthesis in cancer metabolism and tumour development
    Baenke, Franziska
    Peck, Barrie
    Miess, Heike
    Schulze, Almut
    [J]. DISEASE MODELS & MECHANISMS, 2013, 6 (06) : 1353 - 1363
  • [4] Influence of preanalytical sampling conditions on the 1H NMR metabolic profile of human blood plasma and introduction of the Standard PREanalytical Code used in biobanking
    Bervoets, Liene
    Louis, Evelyne
    Reekmans, Gunter
    Mesotten, Liesbet
    Thomeer, Michiel
    Adriaensens, Peter
    Linsen, Loes
    [J]. METABOLOMICS, 2015, 11 (05) : 1197 - 1207
  • [5] Cancer Cell Metabolism: One Hallmark, Many Faces
    Cantor, Jason R.
    Sabatini, David M.
    [J]. CANCER DISCOVERY, 2012, 2 (10) : 881 - 898
  • [6] Study on Metabonomic Characteristics of Human Lung Cancer Using High Resolution Magic-angle Spinning 1H NMR Spectroscopy and Multivariate Data Analysis
    Chen, Wenxue
    Zu, Yukun
    Huang, Qi
    Chen, Fener
    Wang, Guifang
    Lan, Wenxian
    Bai, Chunxue
    Lu, Shaohua
    Yue, Yong
    Deng, Feng
    [J]. MAGNETIC RESONANCE IN MEDICINE, 2011, 66 (06) : 1531 - 1540
  • [7] Metabolomic profiling of human serum in lung cancer patients using liquid chromatography/hybrid quadrupole time-of-flight mass spectrometry and gas chromatography/mass spectrometry
    Chen, Yingrong
    Ma, Zhihong
    Li, Aiying
    Li, Hongwei
    Wang, Bin
    Zhong, Jing
    Min, Lishan
    Dai, Licheng
    [J]. JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, 2015, 141 (04) : 705 - 718
  • [8] Cellular Fatty Acid Metabolism and Cancer
    Currie, Erin
    Schulze, Almut
    Zechner, Rudolf
    Walther, Tobias C.
    Farese, Robert V., Jr.
    [J]. CELL METABOLISM, 2013, 18 (02) : 153 - 161
  • [9] Metabolic profiling of biofluids: potential in lung cancer screening and diagnosis
    Duarte, Iola F.
    Rocha, Claudia M.
    Gil, Ana M.
    [J]. EXPERT REVIEW OF MOLECULAR DIAGNOSTICS, 2013, 13 (07) : 737 - 748
  • [10] Can nuclear magnetic resonance (NMR) spectroscopy reveal different metabolic signatures for lung tumours?
    Duarte, Iola F.
    Rocha, Claudia M.
    Barros, Antonio S.
    Gil, Ana M.
    Goodfellow, Brian J.
    Carreira, Isabel M.
    Bernardo, Joao
    Gomes, Ana
    Sousa, Vitor
    Carvalho, Lina
    [J]. VIRCHOWS ARCHIV, 2010, 457 (06) : 715 - 725