Gene expression of bone morphogenic protein 8B in the primary site, peripheral blood and bone marrow of patients with gastric cancer

Mima,Kosuke; Fukagawa,Takeo; Kurashige,Junji; Takano,Yuki; Uchi,Ryutaro; Ueo,Hiroki; Matsumura,Tae; Ishibashi,Masahisa; Sawada,Genta; Takahashi,Yusuke; Akiyoshi,Sayuri; Eguchi,Hidetoshi; Sudo,Tomoya; Sugimachi,Keishi; Watanabe,Masayuki; Ishii,Hideshi; Mori,Masaki; Baba,Hideo; Sasako,Mitsuru; Mimori,Koshi

doi:10.3892/ol.2013.1392

August 2013 Volume 6 Issue 2

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August 2013 Volume 6 Issue 2

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Article

Gene expression of bone morphogenic protein 8B in the primary site, peripheral blood and bone marrow of patients with gastric cancer

Authors:
- Kosuke Mima
- Takeo Fukagawa
- Junji Kurashige
- Yuki Takano
- Ryutaro Uchi
- Hiroki Ueo
- Tae Matsumura
- Masahisa Ishibashi
- Genta Sawada
- Yusuke Takahashi
- Sayuri Akiyoshi
- Hidetoshi Eguchi
- Tomoya Sudo
- Keishi Sugimachi
- Masayuki Watanabe
- Hideshi Ishii
- Masaki Mori
- Hideo Baba
- Mitsuru Sasako
- Koshi Mimori
View Affiliations / Copyright

Affiliations: Department of Surgery, Kyushu University Beppu Hospital, Beppu, Oita 874-0838, Japan, Gastric Surgery Division, National Cancer Center Hospital, Tokyo 104-0045, Japan, Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860‑8556, Japan, Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka 565‑0871, Japan, Department of Surgery, Hyogo College of Medicine, Hyogo, Honshu 663-8501, Japan
Pages: 387-392
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Published online on: June 12, 2013

https://doi.org/10.3892/ol.2013.1392
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Abstract

The prognosis for individuals that are diagnosed with gastric cancer remains poor due to the high frequency of metastatic disease. In response to tumor‑derived secreted factors, the bone marrow generates a suitable microenvironment for the development of metastasis. However, it is largely unknown whether secreted factors in bone marrow associated with metastatic disease of patients with gastric cancer are present. Secreted factors from the bone marrow of patients with metastatic gastric cancer were identified using a DNA microarray analysis and the mRNA expression levels were investigated in 355 bone marrow, 295 peripheral blood and 144 primary site samples using quantitative PCR (qPCR). Using DNA microarray analysis, the present study identified bone morphogenetic protein 8B (BMP8B) as a secreted signaling molecule in the bone marrow that was associated with the metastatic disease of human gastric cancer. The expression levels of BMP8B in the bone marrow of 355 gastric cancer patients were increased with metastatic disease. A significant correlation was demonstrated between BMP8B mRNA expression in the bone marrow and in the peripheral blood. High BMP8B expression in the bone marrow was associated with the diffuse type of gastric cancer (P=0.009), lymph node metastasis (P=0.009), liver metastasis (P=0.044) and peritoneal dissemination (P<0.001). In the primary site, a multivariate analysis revealed BMP8B mRNA expression as one of the independent prognostic factors of gastric cancer [hazard ratio (HR), 2.066; 95% CI, 1.132‑3.772]. This study suggests that BMP8B, a previously unknown secreted factor in cancer progression, has the potential to be used as a prognostic biomarker. The present study may provide insight into a new mechanism that underlies the dissemination of gastric cancer cells.

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