Abstract 3022: Overexpression of LPCAT1 and concomitant lipid alterations in gastric cancer
Authors: Hirotoshi Kikuchi, Takashi Uehara, Tomohiko Setoguchi, Masayoshi Yamamoto, Manabu Ohta, Kinji Kamiya, Satoshi Baba, Mitsutoshi Setou, Haruhiko Sugimura, Hiroyuki Konno
Journal: Cancer Research (2012)

Abstract Background: Gastric cancer is the second most common neoplasm in the world and the second major cause of cancer death in Japan. Discovery of Helicobacter pylori, one of the major causes of gastric ulcer as well as gastric cancer, has dramatically developed our understanding of pathogenesis in upper gut. Recently, involvement of lipid in the carcinogenic and developmental process has been reported in other malignancies such as colon cancer, but its roles in gastric cancer remain to be analyzed. In this study we utilized imaging mass spectrometry to analyze the alterations of lipid in the gastric cancer specimens. Methods: Twelve sections of human gastric cancer and adjacent normal tissues surgically resected were utilized for the lipid analysis. Mass spectra were acquired using the MALDI-TOF/TOF type mass spectrometer (ultraflex II; Bruker Daltonics), equipped with a 355 nm Nd:YAG laser. A total of 200 laser shots per point were irradiated (1 s/point). Ion images were reconstructed from the spectra with flexImaging 2.1 (Bruker Daltonics). The two-dimensional image obtained was compared to the hematoxylin and eosin staining of a nearby section. The mass spectra were obtained both from cancerous lesion and non-neoplastic mucosa and the structure of lipid molecules was determined using lipid databases such as Lipid Search. Protein expression of lysophosphatidylcholine acyltransferase 1 (LPCAT1) was immunohistochemically analyzed in 196 gastric cancer specimens and corresponding non-cancerous mucosa. Results: The averaged spectra from the whole section, the non-neoplastic area and the cancerous area could be distinguished. All of spectra had a number of signals in the mass range, most of which corresponded to the phospholipids region. Majority of such signals within the phospholipids region were characterized as phosphatidylcholine (PC) and lysophosphatidylcholine (LPC). We focused on two signals: m/z 798.5 and 496.3 which were higher and lower, respectively, in cancer lesion compared with non-neoplastic area. From the results of the database search, we identified the ion at m/z 798.5 and 496.3 as potassium-adducted PC (16:0/18:1) and proton-adducted LPC (16:0), respectively. LPC is known to be converted to PC in the presence of acyl-CoA by LPCAT1 in Lands’ cycle. Immunohistochemical analysis revealed that LPCAT1 was highly expressed in cancer lesion compared with non-neoplastic mucosa and that expression levels of LPCAT1 in cancer lesions were higher in differentiated adenocarcinoma than poorly differentiated adenocarcinoma. Conclusions: Lipid alterations in gastric mucosa appear to be involved in the carcinogenic or developmental process of gastric cancer. In particular, overexpressed LPCAT1 may play important roles by converting LPC to PC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3022. doi:1538-7445.AM2012-3022