Overexpression of Lysophosphatidylcholine Acyltransferase 1 and Concomitant Lipid Alterations in Gastric Cancer

胃癌中溶血磷脂酰胆碱酰基转移酶 1 的过度表达和伴随的脂质改变

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作者:Takashi Uehara, Hirotoshi Kikuchi, Shinichiro Miyazaki, Ichirota Iino, Tomohiko Setoguchi, Yoshihiro Hiramatsu, Manabu Ohta, Kinji Kamiya, Yoshifumi Morita, Hiroki Tanaka, Satoshi Baba, Takahiro Hayasaka, Mitsutoshi Setou, Hiroyuki Konno

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.

Conclusions

Overexpressed LPCAT1 protein in gastric mucosa appears to play important roles in the tumorigenic process of gastric cancer by converting LPC to PC.

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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