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2017 ; 114
(13
): 3334-3339
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Diagnosis of prostate cancer by desorption electrospray ionization mass
spectrometric imaging of small metabolites and lipids
#MMPMID28292895
Banerjee S
; Zare RN
; Tibshirani RJ
; Kunder CA
; Nolley R
; Fan R
; Brooks JD
; Sonn GA
Proc Natl Acad Sci U S A
2017[Mar]; 114
(13
): 3334-3339
PMID28292895
show ga
Accurate identification of prostate cancer in frozen sections at the time of
surgery can be challenging, limiting the surgeon's ability to best determine
resection margins during prostatectomy. We performed desorption electrospray
ionization mass spectrometry imaging (DESI-MSI) on 54 banked human cancerous and
normal prostate tissue specimens to investigate the spatial distribution of a
wide variety of small metabolites, carbohydrates, and lipids. In contrast to
several previous studies, our method included Krebs cycle intermediates (m/z
<200), which we found to be highly informative in distinguishing cancer from
benign tissue. Malignant prostate cells showed marked metabolic derangements
compared with their benign counterparts. Using the "Least absolute shrinkage and
selection operator" (Lasso), we analyzed all metabolites from the DESI-MS data
and identified parsimonious sets of metabolic profiles for distinguishing between
cancer and normal tissue. In an independent set of samples, we could use these
models to classify prostate cancer from benign specimens with nearly 90% accuracy
per patient. Based on previous work in prostate cancer showing that glucose
levels are high while citrate is low, we found that measurement of the
glucose/citrate ion signal ratio accurately predicted cancer when this ratio
exceeds 1.0 and normal prostate when the ratio is less than 0.5. After brief
tissue preparation, the glucose/citrate ratio can be recorded on a tissue sample
in 1 min or less, which is in sharp contrast to the 20 min or more required by
histopathological examination of frozen tissue specimens.