title: Gene expression of bone morphogenic protein 8B in the primary site, peripheral blood and bone marrow of patients with gastric cancer.
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 betweenBMP8BmRNA expression in the bone marrow and in the peripheral blood. HighBMP8Bexpression 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 revealedBMP8BmRNA 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.
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, Beppu, Oita 874-0838, Japan ; ; Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556;
authors.forename: Kosuke
authors.initials: K
authors.lastname: Mima
authors.forename: Takeo
authors.initials: T
authors.lastname: Fukagawa
authors.forename: Junji
authors.initials: J
authors.lastname: Kurashige
authors.forename: Yuki
authors.initials: Y
authors.lastname: Takano
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Uchi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ueo
authors.forename: Tae
authors.initials: T
authors.lastname: Matsumura
authors.forename: Masahisa
authors.initials: M
authors.lastname: Ishibashi
authors.forename: Genta
authors.initials: G
authors.lastname: Sawada
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Sayuri
authors.initials: S
authors.lastname: Akiyoshi
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Eguchi
authors.forename: Tomoya
authors.initials: T
authors.lastname: Sudo
authors.forename: Keishi
authors.initials: K
authors.lastname: Sugimachi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Watanabe
authors.forename: Hideshi
authors.initials: H
authors.lastname: Ishii
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
authors.forename: Hideo
authors.initials: H
authors.lastname: Baba
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Sasako
authors.forename: Koshi
authors.initials: K
authors.lastname: Mimori
keywords: bone marrow; bone morphogenetic protein 8B; gastric cancer