Abstract
Background
The involvement of lipids in carcinogenic and developmental processes has been reported in some malignancies, but their roles in gastric cancer remain to be analyzed. In this study, we compared the lipid content of gastric cancer tissue and adjacent nonneoplastic mucosa using imaging mass spectrometry.
Methods
Mass spectra were acquired from 12 sections of human gastric cancer tissue and adjacent nonneoplastic mucosa using a matrix-assisted laser desorption-ionization time-of-flight tandem mass spectrometry type mass spectrometer equipped with a 355 nm Nd:YAG laser. Protein expression of lysophosphatidylcholine acyltransferase 1 (LPCAT1), which converts lysophosphatidylcholine (LPC) to phosphatidylcholine (PC) in the presence of acyl-CoA in Lands’ cycle, was immunohistochemically analyzed in 182 gastric cancer specimens.
Results
The averaged mass spectra from the cancer tissue and nonneoplastic mucosa were identical. Most of the signals that differed between cancer tissue and nonneoplastic mucosa corresponded to phospholipids, the majority of which were PC and LPC. Two signals, m/z 798.5 and 496.3, were higher and lower, respectively, in cancer tissues, predominantly in differentiated adenocarcinoma. A database search enabled identification of the ions at m/z 798.5 and m/z 496.3 as potassium-adducted PC (16:0/18:1) and proton-adducted LPC (16:0), respectively. Immunohistochemical analysis revealed that LPCAT1 was highly expressed in cancer lesions compared to nonneoplastic mucosa, predominantly in differentiated adenocarcinoma. LPCAT1 expression levels correlated positively with tumor differentiation and negatively with tumor depth, lymph node metastasis, and tumor stage.
Conclusions
Overexpressed LPCAT1 protein in gastric mucosa appears to play important roles in the tumorigenic process of gastric cancer by converting LPC to PC.
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Acknowledgment
This work was supported in part by the Ministry of Education, Culture, Sports, Science, and Technology of Japan Grants-in-Aid 22791270 (H. Kikuchi), 20670004 (M. Setou), and 21390376 (H. Konno), and the Development of System and Technology for Advanced Measurement and Analysis (M. Setou).
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The authors declare no conflict of interest.
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Takashi Uehara and Hirotoshi Kikuchi have contributed equally to this article, and both should be considered first author.
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Uehara, T., Kikuchi, H., Miyazaki, S. et al. Overexpression of Lysophosphatidylcholine Acyltransferase 1 and Concomitant Lipid Alterations in Gastric Cancer. Ann Surg Oncol 23 (Suppl 2), 206–213 (2016). https://doi.org/10.1245/s10434-015-4459-6
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DOI: https://doi.org/10.1245/s10434-015-4459-6