Clinical significance of expression and epigenetic profiling of TUSC1 in gastric cancer.
OBJECTIVE
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.
Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
Mitsuro
M
Kanda
Dai
D
Shimizu
Shuji
S
Nomoto
Soki
S
Hibino
Hisaharu
H
Oya
Hideki
H
Takami
Daisuke
D
Kobayashi
Suguru
S
Yamada
Yoshikuni
Y
Inokawa
Chie
C
Tanaka
Tsutomu
T
Fujii
Hiroyuki
H
Sugimoto
Masahiko
M
Koike
Michitaka
M
Fujiwara
Yasuhiro
Y
Kodera
D000328:Adult; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D018899:CpG Islands; D019175:DNA Methylation; D018450:Disease Progression; D015536:Down-Regulation; D063185:Epigenetic Repression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005819:Genetic Markers; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
D014408:Biomarkers, Tumor; D005819:Genetic Markers; C000591496:TUSC1 protein, human; D025521:Tumor Suppressor Proteins
TUSC1; expression; gastric cancer; intragenic methylation; tumor suppressor