The Expression of Melanoma-Associated Antigen D2 Both in Surgically Resected and Serum Samples Serves as Clinically Relevant Biomarker of Gastric Cancer Progression.
BACKGROUND
Sensitive biomarkers are necessary for risk classification of patients with gastric cancer (GC), especially ones at risk of distant metastases. Melanoma-associated antigen (MAGE)-D2 has been reported to play a role in the process of cell adhesion and metastatic potential of tumor cells in colorectal cancer. The purpose of this study was to identify a novel clinically relevant biomarker of GC.


METHODS
Expression analysis of MAGE-D2 was conducted in GC cell lines and clinical samples (surgical specimen and serum) in both mRNA and protein level. Correlations between MAGE-D2 expression status and clinicopathological factors were evaluated.


RESULTS
MAGE-D2 mRNA expression levels were similar between GC tissues and the corresponding normal adjacent tissues and were independent of GC differentiation or subtype. In 101 (45 %) of 225 patients, the expression level of MAGE-D2 mRNA was increased in GC tissues compared with the corresponding normal adjacent tissues. Increased expression of MAGE-D2 mRNA in GC tissues was associated with distant metastasis and early recurrence and was an independent prognostic factor (hazard ratio 2.27, 95 % confidence interval 1.39-3.74, P = 0.001). There was a stepwise increase in serum MAGE-D2 level going from healthy volunteers to patients with localized GC and then to those with extended GC (stage IV). Patients with preoperative serum MAGE-D2 levels >130 pg/ml had a more unfavorable prognosis than those with levels ≤130 pg/ml.


CONCLUSIONS
MAGE-D2 was associated with metastatic potential of GC and may represent a promising biomarker, both in gastric tissues and serum samples, for malignant behavior of GC.
Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan. m-kanda@med.nagoya-u.ac.jp.
Mitsuro
M
Kanda
Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
Shuji
S
Nomoto
Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
Hisaharu
H
Oya
Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
Hideki
H
Takami
Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
Dai
D
Shimizu
Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
Soki
S
Hibino
Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
Ryoji
R
Hashimoto
Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
Daisuke
D
Kobayashi
Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
Chie
C
Tanaka
Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
Suguru
S
Yamada
Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
Tsutomu
T
Fujii
Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
Goro
G
Nakayama
Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
Hiroyuki
H
Sugimoto
Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
Masahiko
M
Koike
Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
Michitaka
M
Fujiwara
Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
Yasuhiro
Y
Kodera
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000556:secondary / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D013270:Stomach; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D015996:Survival Rate; D055815:Young Adult
D048868:Adaptor Proteins, Signal Transducing; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C451414:MAGED2 protein, human