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

Abstract

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-IMS) 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.

The lysophospholipase D enzyme Gdpd3 is required to maintain chronic myelogenous leukaemia stem cells

“…It is known that ATX -disrupted mice exhibit embryonic lethality, and that enforced expression of ATX or LPARs promotes the initiation and metastasis of breast cancer in transgenic mouse strains 12 , 13 . In humans, our knowledge is even more limited, although aberrant expression of phosphatidylcholines (PCs) has been detected in patients with colorectal cancer, triple-negative breast cancer, or lung adenocarcinoma 14 – 16 .…”

Trans‐omic profiling between clinical phenoms and lipidomes among patients with different subtypes of lung cancer

“…26 The monounsaturated/saturated PC ratios were proposed to distinguish ADC histologic subtype-dependent variations among lepidic, acinar, papillary, micropapillary, solid, and mucinous phenomes. 27 The heterogeneity of lipidomic profiles and lipid metabolism could impact the specificity for lung cancer subtype, severity, stage, and drug efficacy, although characteristics of lipidomic profiles of lung cancer subtypes varied among studies because of different subjects, designs, methods, and analyses. 8 In addition, multiple factors of lung cancer patients, for example, age, gender, stages, metastatic status, body condition, and clinical phenotyping, should be considered to evaluate values of lipidomic profiles.…”

“…The specificity of human breast cancer cell subtypes was also noticed by measuring the quantitation of lipid C = C location and sn‐position structure isomers 26 . The monounsaturated/saturated PC ratios were proposed to distinguish ADC histologic subtype‐dependent variations among lepidic, acinar, papillary, micropapillary, solid, and mucinous phenomes 27 . The heterogeneity of lipidomic profiles and lipid metabolism could impact the specificity for lung cancer subtype, severity, stage, and drug efficacy, although characteristics of lipidomic profiles of lung cancer subtypes varied among studies because of different subjects, designs, methods, and analyses 8 …”

Tissue fixation effects on human retinal lipid analysis by MALDI imaging and LC-MS/MS technologies

“…The majority of lipids discovered in both fresh-frozen and fixed tissues were glycerophospholipids, followed by glycerolipids, sphingolipids and cholesteryl esters. The highest number of detected lipid subclasses were diacylglycerophosphocholines (PC, 124), triacylglycerol (TG, 94), sphingomyelins (SM, 42), and cholesteryl esters (CE,9). There were 352 glycerophospholipids in fresh-frozen and 250 in fixed tissue representing a 29% decrease, covering lipid subclasses including, PC, PI, PG, PE, PS, plasmalogen lipids and lyso phospholipids.…”

“…[1][2][3][4] In contrast, LC-MS/MS facilitates structural elucidation by generating molecularly-specific fragmentation spectra. [1][2][3]5,6 Combining analyte localization with accurate mass measurements from MALDI-IMS 2,7,8 with structural characterization by LC-MS/MS 7,9 greatly enhances the breadth and depth of analysis of a tissue lipidome. [10][11][12] MALDI-IMS analysis is typically done directly on fresh-frozen tissue sections so as to avoid chemical alterations.…”