Novel non-invasive early detection of lung cancer using liquid immunobiopsy metabolic activity profiles

Cancer Immunol Immunother. 2018 Jul;67(7):1135-1146. doi: 10.1007/s00262-018-2173-5. Epub 2018 May 21.


Lung cancer is the leading cause of cancer death worldwide. Survival is largely dependent on the stage of diagnosis: the localized disease has a 5-year survival greater than 55%, whereas, for spread tumors, this rate is only 4%. Therefore, the early detection of lung cancer is key for improving prognosis. In this study, we present an innovative, non-invasive, cancer detection approach based on measurements of the metabolic activity profiles of immune system cells. For each Liquid ImmunoBiopsy test, a 384 multi-well plate is loaded with freshly separated PBMCs, and each well contains 1 of the 16 selected stimulants in several increasing concentrations. The extracellular acidity is measured in both air-open and hermetically-sealed states, using a commercial fluorescence plate reader, for approximately 1.5 h. Both states enable the measurement of real-time accumulation of 'soluble' versus 'volatile' metabolic products, thereby differentiating between oxidative phosphorylation and aerobic glycolysis. The metabolic activity profiles are analyzed for cancer diagnosis by machine-learning tools. We present a diagnostic accuracy study, using a multivariable prediction model to differentiate between lung cancer and control blood samples. The model was developed and tested using a cohort of 200 subjects (100 lung cancer and 100 control subjects), yielding 91% sensitivity and 80% specificity in a 20-fold cross-validation. Our results clearly indicate that the proposed clinical model is suitable for non-invasive early lung cancer diagnosis, and is indifferent to lung cancer stage and histological type.

Keywords: Cancer diagnosis; Early detection; Liquid biopsy; Lung cancer; Metabolic profile.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Case-Control Studies
  • Early Detection of Cancer / methods*
  • Female
  • Follow-Up Studies
  • Humans
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / surgery
  • Male
  • Metabolome*
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Young Adult


  • Biomarkers, Tumor