Pathologic staging of renal clear cell carcinoma (ccRCC) provides useful but limited prognostic information suggesting that there are underlying molecular processes not readily identified through conventional histopathological techniques in the primary tumor. At the molecular level, transcript, metabolomic and protein expression patterns have indicated a striking Warburg Effect profile in ccRCC tissues, with major affects on sugar and lipid metabolism. Our group has been applying MALDI-MS imaging approaches to ccRCC tissues to profile lipids and glycans associated with disease progression. As both lipids and glycans can act as signaling molecules and have been associated with cancer progression, ccRCC tissues were selected by a pathologist to contain substantial tumor, non-tumor and tumor margin regions to characterize the differential localization of lipid and glycan species within the tissue. Lipid profiles from fresh-frozen tissue slides coated in DHB matrix were obtained on a dual source Bruker Solarix 70 FTICR mass spectrometer. Glycans were imaged in a similar fashion with a method developed by our lab using protein N-glycanase F to release protein bound N-glycans. There are clear patterns of specific lipid and glycan species that are only present along the margin of the tumor and non-tumor interface, or those primarily localized in non-tumor or tumor regions. Off-tissue extraction of lipids and glycans from similarly processed tissues and further mass spectrometry analysis was done to confirm structural designations. Linkage of differentially expressed lipid and glycan species with clinical data and other molecular markers of ccRCC is ongoing. This approach has the potential to not only improve prognostic assessment and enhance post-operative surveillance, but also to better define the underlying biology of ccRCC aggressiveness and identify new rational targets for therapeutic intervention.

Citation Format: Richard R. Drake, Thomas Powers, Ellen Jones, Raymond S. Lance, Anand S. Mehta, Dean A. Troyer. MALDI mass spectrometry imaging for on-tissue spatial profiling of tumor-specific N-linked glycans and lipids in renal carcinomas. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1523. doi:10.1158/1538-7445.AM2013-1523