The Ratios of monounsaturated to saturated phosphatidylcholines in lung adenocarcinoma microenvironment analyzed by Liquid Chromatography-Mass spectrometry and imaging Mass spectrometry

Adenocarcinoma is the most common type of lung cancer, and can be classified into various histologic subtypes. However, little is known about the subtype-dependent variations in lipid metabolism processes. We performed dual lipidomic analyses using liquid chromatography-mass spectrometry (LC-MS) and matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-I MS) to identify possible biomarkers to distinguish adenocarcinoma specimens from normal lung specimens, and to determine if there are any differences in lipid metabolism among the histologic subtypes (lepidic, acinar, papillary, micropapillary, solid, and mucinous). LC-MS was used to characterize the lipid profiles of lung adenocarcinoma and normal lung tissue, and MALDI-IMS analysis was performed to confirm the results with information on lipid localization within the lung. LC-MS analysis found significant differences in the relative abundances of phosphatidylcholine (PC)(16:0/16:0) (P = 0.0432) and sphingomyelin (SM)(42:2) (P < 0.0001) between adenocarcinoma and normal lung specimens. The ratios of PC(16:0/16:1)/PC(16:0/16:0), PC(16:0/18:1/PC(16:0/16:0), and PC(16:0/18:1)/PC(16:0/18:0) were significantly higher in adenocarcinoma specimens (P= 0.02221, P= 0.0004, and P= 0.0215, respectively). MALDI-IMS analysis confirmed that these ratios were significantly higher in adenocarcinoma regions of the lung. The ratio of PC(16:0-18:1)/PC(16:0-18:0) was significantly lower in solid subtypes than in other subtypes (P = 0.0028). The monounsaturated/saturated PC ratios may have applications in adenocarcinoma diagnoses and subtyping.