Multivariate statistical differentiation of renal cell carcinomas based on lipidomic analysis by ambient ionization imaging mass spectrometry.
Desorption electrospray ionization (DESI) mass spectrometry (MS) was used in an imaging mode to interrogate the lipid profiles of thin tissue sections of 11 sample pairs of human papillary renal cell carcinoma (RCC) and adjacent normal tissue and nine sample pairs of clear cell RCC and adjacent normal tissue. DESI-MS images showing the spatial distributions of particular glycerophospholipids (GPs) and free fatty acids in the negative ion mode were compared to serial tissue sections stained with hematoxylin and eosin (H&E). Increased absolute intensities as well as changes in relative abundance were seen for particular compounds in the tumor regions of the samples. Multivariate statistical analysis using orthogonal projection to latent structures treated partial least square discriminate analysis (PLS-DA) was used for visualization and classification of the tissue pairs using the full mass spectra as predictors. PLS-DA successfully distinguished tumor from normal tissue for both papillary and clear cell RCC with misclassification rates obtained from the validation set of 14.3% and 7.8%, respectively. It was also used to distinguish papillary and clear cell RCC from each other and from the combined normal tissues with a reasonable misclassification rate of 23%, as determined from the validation set. Overall DESI-MS imaging combined with multivariate statistical analysis shows promise as a molecular pathology technique for diagnosing cancerous and normal tissue on the basis of GP profiles.
Department of Chemistry and Center for Analytical Instrumentation Development, Purdue University, West Lafayette, IN 47907, USA.
Allison L
AL
Dill
Livia S
LS
Eberlin
Cheng
C
Zheng
Anthony B
AB
Costa
Demian R
DR
Ifa
Liang
L
Cheng
Timothy A
TA
Masterson
Michael O
MO
Koch
Olga
O
Vitek
R Graham
RG
Cooks
D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D003952:Diagnostic Imaging / Q000379:methods*; D005230:Fatty Acids, Nonesterified / Q000032:analysis / Q000378:metabolism*; D020404:Glycerophospholipids / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D015999:Multivariate Analysis; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods* / Q000592:standards
D005230:Fatty Acids, Nonesterified; D020404:Glycerophospholipids