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The Expression of Melanoma-Associated Antigen D2 Both in Surgically Resected and Serum Samples Serves as Clinically Relevant Biomarker of Gastric Cancer Progression

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

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.

Conclusion

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.

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Authors and Affiliations

  1. Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan

    Mitsuro Kanda MD, PhD, Shuji Nomoto MD, PhD, Hisaharu Oya MD, Hideki Takami MD, Dai Shimizu MD, Soki Hibino MD, Ryoji Hashimoto MD, Daisuke Kobayashi MD, PhD, Chie Tanaka MD, PhD, Suguru Yamada MD, PhD, FACS, Tsutomu Fujii MD, PhD, FACS, Goro Nakayama MD, PhD, Hiroyuki Sugimoto MD, PhD, Masahiko Koike MD, PhD, Michitaka Fujiwara MD, PhD & Yasuhiro Kodera MD, PhD, FACS

Authors
  1. Mitsuro Kanda MD, PhD
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  2. Shuji Nomoto MD, PhD
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  3. Hisaharu Oya MD
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  4. Hideki Takami MD
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  7. Ryoji Hashimoto MD
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  8. Daisuke Kobayashi MD, PhD
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  9. Chie Tanaka MD, PhD
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  10. Suguru Yamada MD, PhD, FACS
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  13. Hiroyuki Sugimoto MD, PhD
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  14. Masahiko Koike MD, PhD
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  15. Michitaka Fujiwara MD, PhD
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  16. Yasuhiro Kodera MD, PhD, FACS
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Corresponding author

Correspondence to Mitsuro Kanda MD, PhD.

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10434_2015_4457_MOESM1_ESM.tif

(a) Expression status of MAGE-D2 mRNA in GC cell lines. Error bars indicated standard deviation of biologic replicates tested in triplicate. (b, c) Expression status of MAGE-D2 mRNA in clinical specimens. (b) MAGE-D2 mRNA expression level was equivalent between GC tissues and the corresponding normal adjacent tissues regardless of GC differentiation. ( c) Comparison of MAGE-D2 mRNA expression levels between GC tissues and the corresponding normal adjacent tissues for each GC subtype. No differences were shown for any GC subtype. NS, not significant (TIFF 6924 kb)

10434_2015_4457_MOESM2_ESM.tif

Kaplan–Meier curves comparing survival of patients with and without downregulation of MAGE-D2 mRNA for each GC subtype. Survival difference is shown for the distal nondiffuse GC subtype (TIFF 6925 kb)

10434_2015_4457_MOESM3_ESM.tif

Prevalence of (a) lymph node metastasis and (b) distant metastasis categorized by gastric cancer subtype and MAGE-D2 expression status. NS, not significant (TIFF 6924 kb)

Supplementary material 4 (DOC 11 kb)

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Kanda, M., Nomoto, S., Oya, H. et al. The Expression of Melanoma-Associated Antigen D2 Both in Surgically Resected and Serum Samples Serves as Clinically Relevant Biomarker of Gastric Cancer Progression. Ann Surg Oncol 23 (Suppl 2), 214–221 (2016). https://doi.org/10.1245/s10434-015-4457-8

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  • DOI: https://doi.org/10.1245/s10434-015-4457-8

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