Overexpression of Lysophosphatidylcholine Acyltransferase 1 and Concomitant Lipid Alterations in Gastric Cancer.
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.
Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Takashi
T
Uehara
Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan. kikuchih@hama-med.ac.jp.
Hirotoshi
H
Kikuchi
Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Shinichiro
S
Miyazaki
Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Ichirota
I
Iino
Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Tomohiko
T
Setoguchi
Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Yoshihiro
Y
Hiramatsu
Oncology Center, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Manabu
M
Ohta
Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Kinji
K
Kamiya
Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Yoshifumi
Y
Morita
Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Hiroki
H
Tanaka
Department of Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Satoshi
S
Baba
Department of Cell Biology and Anatomy, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Takahiro
T
Hayasaka
Department of Cell Biology and Anatomy, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Mitsutoshi
M
Setou
Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Hiroyuki
H
Konno
D008243:1-Acylglycerophosphocholine O-Acyltransferase / Q000378:metabolism*; D000230:Adenocarcinoma / Q000378:metabolism / Q000556:secondary* / Q000601:surgery; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008244:Lysophosphatidylcholines / Q000378:metabolism*; D008297:Male; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010713:Phosphatidylcholines / Q000378:metabolism*; D011379:Prognosis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D015996:Survival Rate
D014408:Biomarkers, Tumor; D008244:Lysophosphatidylcholines; D010713:Phosphatidylcholines; D008243:1-Acylglycerophosphocholine O-Acyltransferase; C526202:Lpcat1 protein, human