Document Detail


Prognostic impact of expression and methylation status of DENN/MADD domain-containing protein 2D in gastric cancer.
MedLine Citation:
PMID:  24695972     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 (DENND2D), 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.
Authors:
Mitsuro Kanda; Dai Shimizu; Shuji Nomoto; Hideki Takami; Soki Hibino; Hisaharu Oya; Ryoji Hashimoto; Masaya Suenaga; Yoshikuni Inokawa; Daisuke Kobayashi; Chie Tanaka; Suguru Yamada; Tsutomu Fujii; Goro Nakayama; Hiroyuki Sugimoto; Masahiko Koike; Michitaka Fujiwara; Yasuhiro Kodera
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-4-3
Journal Detail:
Title:  Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association     Volume:  -     ISSN:  1436-3291     ISO Abbreviation:  Gastric Cancer     Publication Date:  2014 Apr 
Date Detail:
Created Date:  2014-4-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100886238     Medline TA:  Gastric Cancer     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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