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

Yusuke Muranishi,Junko Satoh,Akihiko Yoshizawa,Shigeyuki Tamari,Toshi Menju,Yojiro Yutaka,Yuichiro Ueda,Toshihiko Sato,Tatsuo Nakamura,Hiroshi Date,Shinji Ito

doi:10.1038/s41598-019-45506-3

Yusuke Muranishi, Junko Satoh + Show 9 more

Open Access

https://doi.org/10.1038/s41598-019-45506-3

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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.

Highlights

Lung cancer is a major cause of cancer-related death throughout the world, and is often associated with a poor prognosis
We conducted a comprehensive investigation of the lipid profiles of lung adenocarcinoma and normal lung specimens using liquid chromatography–MS (LC-MS)
The S-plot of the orthogonal projections to latent structures discriminant analysis (OPLS-DA) revealed abundant ions at m/z 782.57 and m/z 760.58 in the adenocarcinoma specimens, whereas ions at m/z 734.57 and m/z 813.68 were more abundant in the normal lung specimens (Fig. 1A) We show the scores plot for OPLS-DA (Fig. 1B)

Summary

Introduction

Lung cancer is a major cause of cancer-related death throughout the world, and is often associated with a poor prognosis. In 2011, the International Association for the Study of Lung Cancer, the American Thoracic Society, and the European Respiratory Society collaboratively developed a classification scheme to standardize the diagnostic criteria for lung adenocarcinomas[3]. In this system, lung adenocarcinomas are histologically classified into atypical adenomatous hyperplasia, adenocarcinomas in situ, minimally invasive adenocarcinomas, and invasive adenocarcinomas. We conducted a comprehensive investigation of the lipid profiles of lung adenocarcinoma and normal lung specimens using liquid chromatography–MS (LC-MS). These results were revaluated and confirmed using matrix-assisted laser desorption/ionization imaging MS (MALDI-IMS) supplemented with information on the lung localization of each lipid

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