Dihydropyrimidinase-like 3 facilitates malignant behavior of gastric cancer

Mitsuro Kanda(Nagoya University), Shuji Nomoto(Nagoya University), Hisaharu Oya(Nagoya University), Dai Shimizu(Nagoya University), Hideki Takami(Nagoya University), Soki Hibino(Nagoya University), Ryoji Hashimoto(Nagoya University), Daisuke Kobayashi(Nagoya University), Chie Tanaka(Nagoya University), Suguru Yamada(Nagoya University), Tsutomu Fujii(Nagoya University), Goro Nakayama(Nagoya University), Hiroyuki Sugimoto(Nagoya University), Masahiko Koike(Nagoya University), Michitaka Fujiwara(Nagoya University), Yasuhiro Kodera(Nagoya University)
Journal of Experimental & Clinical Cancer Research
August 5, 2014
Cited by 65Open Access
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Abstract

BACKGROUND: Gastric cancer (GC) remains to have a poor prognosis via diverse process of cancer progression. Dihydropyrimidinase-like 3 (DPYSL3) is a cell adhesion molecule that has been reported to be involved in the metastatic process of tumor cells. The aim of this study was to identify a novel clinically-relevant biomarker of GC. METHODS: Expression analysis of DPYSL3 mRNA and protein levels was conducted using GC cell lines and 238 pairs of surgically resected gastric tissues. Correlations between expression status of DPYSL3 and clinicopathological parameters were investigated. RESULTS: DPYSL3 mRNA expression levels positively correlated with those of potentially interacting genes (VEGF, FAK and EZR) in GC cell lines. GC tissues from tumors with distant metastases (stage IV cancer) showed elevated expression levels of DPYSL3 mRNA. The DPYSL3 staining intensity in immunochemical staining was consistent with the mRNA expression patterns in GC tissues. High DPYSL3 mRNA expression in GCs was significantly associated with more malignant phenotypes and was an independent prognostic factor. Moreover, patients with high DPYSL3 mRNA expression had a significantly shorter recurrence free survival after curative resection. In subgroup analysis based on tumor histology, similar tendency was observed between patients with differentiated and undifferentiated GCs. CONCLUSIONS: Expression status of DPYSL3 in GC tissues may represent a promising biomarker for the malignant behavior of GC.


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