Dataset Information

Dihydropyrimidinase-like 3 facilitates malignant behavior of gastric cancer.

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.

SUBMITTER: Kanda M

PROVIDER: S-EPMC4431488 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Publications

Dihydropyrimidinase-like 3 facilitates malignant behavior of gastric cancer.

Kanda Mitsuro M Nomoto Shuji S Oya Hisaharu H Shimizu Dai D Takami Hideki H Hibino Soki S Hashimoto Ryoji R Kobayashi Daisuke D Tanaka Chie C Yamada Suguru S Fujii Tsutomu T Nakayama Goro G Sugimoto Hiroyuki H Koike Masahiko M Fujiwara Michitaka M Kodera Yasuhiro Y

Journal of experimental & clinical cancer research : CR 20140806

<h4>Background</h4>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.<h4>Methods</h4>Expression analysis of DPYSL3 mRNA and protein levels was conducted using GC cell lines and 238 pairs of surgically resected gastric tissues. C ...[more]

PMID: 25096402

Similar Datasets

Project description:BackgroundThe incidence of gastric cancer (GC) ranks fourth among all malignant tumors worldwide, and the fatality rate ranks second among all malignant tumors. Several Chinese traditional medicines have been used in the treatment of advanced gastric cancer. This study aims to investigate the effect of combinational use of natural product cryptotanshinone (CTS) with anti-cancer drug trifluorothymidine (FTD) in GC.MethodsCell Counting Kit-8 assay was used to detect the inhibitory effect of the combinational or separate use of FTD and CTS on the growth of HGC-27 and AGS GC cells. The combined index of FTD and CTS was calculated using CompuSyn software. To understand the mechanism, we applied flow cytometry to study the cell cycle and cell apoptosis after treatment. We also investigated the amount of FTD incorporated into the DNA by immunofluorescence assay. The expression of relevant proteins was monitored using western blot. Furthermore, the effect of using TAS-102 in combination with CTS was studied in xenograft tumor nude mice model.ResultsFTD and CTS inhibited the growth of GC cells in a dose-dependent manner, respectively. They both exhibited low to sub-micromolar potency in HGC-27 and AGS cells. The combination of FTD and CTS showed synergistic anticancer effect in HGC-27 cells and AGS cells. Our mechanism studies indicate that FTD could block HGC-27 cells at G2/M phase, while CTS could block HGC-27 cells at G1/G0 phase, while FTD combined with CTS could mainly block HGC-27 cells at G2 phase. FTD in combination with CTS significantly increased the apoptosis of HGC-27 cells. We observed that CTS treatment increased the incorporation of FTD into the DNA HGC-27 cell. FTD treatment activated STAT3 phosphorylation in HGC-27 cells, while CTS treatment down-regulated the concentration of p-STAT3. Interestingly, the combination of CTS and FTD reduced STAT3 phosphorylation induced by FTD. In the in vivo experiments, we observed that the combination of TAS-102 with CTS was significantly more potent than TAS-102 on tumor growth inhibition.ConclusionsFTD combined with CTS has a synergistic anti-gastric cancer effect as shown by in vitro and in vivo experiments, and the combined treatment of FTD and CTS will be a promising treatment option for advanced gastric cancer.

Dataset Information

Dihydropyrimidinase-like 3 facilitates malignant behavior of gastric cancer.

Background

Methods

Results

Conclusions

Publications

Dihydropyrimidinase-like 3 facilitates malignant behavior of gastric cancer.

Similar Datasets

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