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W. Cookson

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    MA 06 - Lung Cancer Biology I (ID 660)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Biology/Pathology
    • Presentations: 1
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      MA 06.13 - Direct Metabolomic Profiling of Lung Cancers (ID 10319)

      15:45 - 17:30  |  Author(s): W. Cookson

      • Abstract
      • Presentation
      • Slides

      Lung cancers rely on metabolites to fuel growth and to signal to surrounding tissues. Systematic study of these molecules may identify biomarkers for early diagnosis and novel pathways tractable to therapy. Previous studies of the metabolome in lung cancer have been confined to the serum and to sputum. We have therefore interrogated biochemical profiles in human lung cancers and matched adjacent normal tissues with the aim of identifying metabolites and metabolic signatures associated with lung cancer.

      Global biochemical profiles were determined in human lung tumour and adjacent normal tissue. 12 tumours and 12 matched normal samples were tested from adenocarcinoma (ADC) patients, and 12 tumour/normal pairs were similarly tested from squamous cell carcinoma (SCC) patients. Samples were analysed on the Metabolon GC/MS and LC/MS/MS platforms, with the inclusion of technical replicates.

      Application of PCA as a function of the tissue metabolome demonstrated that the normal, ADC and SCC groups were clearly distinguishable. We observed general metabolic changes associated with tumour tissue (q<0.10 throughout), with reductions in glucose and concomitant elevations in sorbitol and lactate indicative of Warburg metabolism in both ADC and SCC. Levels of reduced glutathione (GSH) were higher in SCC compared to ADC and normal tissue, indicating elevated antioxidant capacity in SCC. Conversely, alternative antioxidants including taurine, biliverdin, ascorbate, alpha- and gamma-tocopherol, and ergothioneine were higher in ADC than SCC. The neurotransmitters serine, NAA, GABA, and NAAG were also significantly elevated in ADC but not SCC. Finally, elevations in prostaglandin D2 and 6-keto prostaglandin F1alpha were confined to SCC and prostaglandin E2 was elevated to a much greater extent (8-fold versus 3-fold) in SCC vs. ADC, as compared respectively to normal lung tissue.

      Results from this pilot global profiling study confirm greater glucose utilization and lactate production, increased fatty acid synthesis, and changes in membrane biology in ADC and SCC. However, changes in glutathione metabolism, antioxidant capacity, neuroactive metabolites, and inflammation appear to vary according to tumour type. A larger scale study may identify differential therapeutic avenues and response to therapy. Profiling of matched serum/plasma from lung cancer patients may allow for identification of disease-specific biomarkers to supplement histological-based diagnostic techniques.

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