Prognostic impact of expression and methylation status of DENN/MADD domain-containing protein 2D in gastric cancer

Abstract

Background Patients with advanced gastric cancer (GC) have an adverse prognosis even after curative resection. Development of novel diagnostic and therapeutic approaches for GC is urgently required. Methods The expression and methylation status of DENN/MADD domain-containing protein 2D (DEN-ND2D), a member of the membrane trafficking proteins, were evaluated in 12 GC cell lines and 112 pairs of surgical specimens. Subgroup analysis based on tumor differentiation, location, and morphology was also performed. Expression and distribution of DENND2D protein were determined by immunohistochemistry. Results The majority of GC cell lines (75 %) and tissues (79 %) showed reduced expression of DENND2D mRNA compared with noncancerous gastric tissues. GC tissues showed a significantly lower mean expression level of mRNA and a higher frequency of promoter hypermethylation of DENND2D than corresponding noncancerous tissues. No significant differences in DENND2D mRNA expression and methylation status were found between GC subtypes categorized by tumor differentiation, location, and morphology. The expression patterns of DENND2D protein were confirmed to be consistent with those of DENND2D mRNA. Downregulation of DENND2D mRNA in GC tissues was significantly associated with factors related to more advanced GC and subsequent adverse prognosis. Among 72 patients who underwent R0 resection, downregulation of DENND2D mRNA in GC tissues was an independent prognostic factor and associated with early recurrence. Conclusions Our results suggested that DENND2D is a putative tumor suppressor gene regulated by promoter hypermethylation in GC. Downregulation of DENND2D can serve as a novel tumor biomarker to predict progression and early recurrence of all types of GC.

Rewired Metabolism in Drug-resistant Leukemia Cells

“…However, DENND2D overexpression suppressed the proliferation of non-small cell lung cancer cells in vitro and in vivo by inducing apoptosis (40), implying that its non-expression in the CEM/R2 cells may represent the loss of a tumor suppressing protein. In keeping with this suggestion, it has been proposed that DENND2D could be a useful marker for predicting the progression and early recurrence of all types of gastric cancer (41). Finally, GLUL transcripts were only detected in CEM cells.…”

Protein arginine methyltransferase 5 is associated with malignant phenotype and peritoneal metastasis in gastric cancer

“…Ten GC cell lines (AGS, KATOIII, MKN1, MKN45, MKN74, N87, NUGC2, NUGC3, NUGC4 and SC-6-JCK) and the non-tumourigenic epithelial cell line (FHs74) were obtained from the American Type Culture Collection (ATCC; Manassas, VA, USA), Tohoku University, Japan, or were established at our institute. Cell lines were cultured at 37˚C in Dulbecco's modified Eagle's medium (DMEM; Sigma-Aldrich, St. Louis, MO, USA) supplemented with 10% fetal bovine serum (FBS) in an atmosphere containing 5% CO 2 (21). Primary GC tissues and the corresponding non-cancerous adjacent tissues were collected from 179 patients who underwent gastric resection for GC without neoadjuvant therapy at Nagoya University Hospital between 2001 and 2010.…”

Effect of urokinase-type plasminogen activator system in gastric cancer with peritoneal metastasis

“…However, in China, even following curative resection, patients with advanced gastric cancer continue to have an adverse prognosis (2). The current medical management of patients with gastric cancer is not satisfactory, and the great expense of the treatment places a large economic burden on the family of the patient and on society.…”