Discovery of Potential Lipid Biomarkers for Human Colorectal Cancer by In-Capillary Extraction Nanoelectrospray...

Discovering cancer biomarkers is of significance for clinical medicine and disease diagnosis. In this article, we develop an in-capillary extraction nanoelectrospray ionization mass spectrometry (ICE-nanoESI-MS) method to rapidly and in situ investigate human colorectal cancer for discovering lipid biomarkers. The ICE-nanoESI-MS method is performed using a tungsten microdissecting probe for in situ microsampling of surgical human colorectal cancer tumors and their paired distal noncancerous tissues during/after surgery. After sampling, the tungsten probe and the adhered tissues are inserted into a nanospray tip prefilled with some solvent for simultaneous in-capillary extraction and nanoESI-MS detection under ambient and open-air conditions. Online coupling of the Paternò-Büchi reaction and radical-direct fragmentation with ICE-nanoESI-MS is easily realized, which provides the opportunity to precisely determine carbon-carbon double bond (C═C) locations and stereospecific numbering (sn) positions of lipid biomarkers. Subsequently, a total of 12 pairs of colorectal cancer tumors and distal noncancerous tissues from different patients are investigated by our proposed ICE-nanoESI-MS method. A significant increase in lysophospholipids and fatty acids as well as a significant decrease in ceramides are discovered, and lysophospholipids are found as the potential biomarkers related to the formation and pathogenesis of human colorectal cancer.