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Clinical significance of expression and epigenetic profiling of TUSC1 in gastric cancer
Author(s) -
Kanda Mitsuro,
Shimizu Dai,
Nomoto Shuji,
Hibino Soki,
Oya Hisaharu,
Takami Hideki,
Kobayashi Daisuke,
Yamada Suguru,
Inokawa Yoshikuni,
Tanaka Chie,
Fujii Tsutomu,
Sugimoto Hiroyuki,
Koike Masahiko,
Fujiwara Michitaka,
Kodera Yasuhiro
Publication year - 2014
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.23614
Subject(s) - dna methylation , immunohistochemistry , methylation , epigenetics , medicine , messenger rna , cancer research , cancer , downregulation and upregulation , metastasis , pathology , gene expression , microbiology and biotechnology , gene , biology , genetics
Background and Objectives The prognosis of advanced gastric cancer (GC) remains dismal. The aim of this study was to identify a novel tumor suppressor gene (TSG) with repressed transcription by aberrant DNA methylation in GC. Methods The expression and methylation status of tumor suppressor candidate 1 ( TUSC1 ) were evaluated in GC cell lines and 112 pairs of surgical specimens. TUSC1 protein expression and distribution in GC tissue were determined by immunohistochemistry. Results The majority of GC cell lines (83%) and GC tissues (82%) showed downregulation of TUSC1 mRNA compared with noncancerous tissues. No significant differences were found in TUSC1 mRNA expression between three GC subtypes categorized by tumor locations and morphology. Reduced expression of TUSC1 mRNA in GC tissues was significantly associated with advanced T stage, vessel invasion and lymph node metastasis, leading to poor prognosis. The expression patterns of TUSC1 protein were confirmed to be consistent with those of TUSC1 mRNA. Sixty‐three (57%) of 112 patients showed intragenic hypermethylation of TUSC1 in GC tissues. Conclusions Our results suggested that reduced expression of TUSC1 mRNA was related to poor prognosis and TUSC1 is a putative TSG that is suppressed through intragenic hypermethylation in GC. J. Surg. Oncol. 2014; 110:136–144 . © 2014 Wiley Periodicals, Inc.