Global change in metabolism is a hallmark feature of neoplasia. Prostate cancer exhibits alterations in lipid metabolism caused by the dysregulation of lipogenic enzymes. Metabolic defect is also resulted by the plethora of the dysregulation of a number of Krebs cycle enzymes, showing significant changes in production of small metabolites and biosynthetic intermediates. Desorption electrospray ionization mass spectrometric imaging (DESI-MSI) is a powerful emerging analytical technique that enables simultaneous visualization of the distribution of hundreds of metabolites/lipids in biologic tissues. We employed this technique on 54 banked human cancerous and benign prostate tissue samples to investigate the differential distribution of different classes of complex lipids (fatty acids, phosphatidic acids, glycerophospholipids <i>etc.</i>) and small molecules (glucose, Krebs cycle metabolites <i>etc.</i>) in normal and cancerous tissue sections. The statistical method of least absolute shrinkage and selection operator (Lasso) was applied to the recorded DESI mass spectra yielding a model with parsimonious sets of metabolite/lipid profiles for distinguishing between cancer and normal tissue. Based on this method, we found nearly 90% overall accuracy in classifying the prostatic tissue as cancer or benign. We also found an impressive capability of glucose and citrate constituents of tissues to detect cancer. When we took the ratio of ion signals of glucose and citrate (glucose/citrate) and constructed the image of that ratio, we found that this ratio has the potential to determine cancer margins accurately. We are extensively investigating the implication of this ratio in determining cancer margin, especially in selective ion monitoring mode in DESI-MSI, that will monitor only glucose and citrate ion selectively, and thus would reduce the image recording time to ~5 minutes or less. Our initial study, as validated by histopathology, determined that if glucose/citrate ratio &gt; 1, we can classify the tissue as cancerous (~100% accuracy) from the corresponding DESI-MS image. These results collectively suggest that lipidomic and small metabolite analysis by DESI-MSI could be a valuable tool for prostate cancer diagnosis.

Mass spectrometric imaging of prostate biopsy samples: Cancer margin assessment from the distribution of small metabolites and lipids

253rd National Meeting (2017)

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