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

Gene expression of bone morphogenic protein 8B in the primary site, peripheral blood and bone marrow of patients with gastric cancer.
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DOI:
10.3892/ol.2013.1392
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发表时间:
2013-08
期刊:
影响因子:
2.9
通讯作者:
Mimori K
Mimori K
中科院分区:
医学4区
文献类型:
--
作者:
Mima K;Fukagawa T;Kurashige J;Takano Y;Uchi R;Ueo H;Matsumura T;Ishibashi M;Sawada G;Takahashi Y;Akiyoshi S;Eguchi H;Sudo T;Sugimachi K;Watanabe M;Ishii H;Mori M;Baba H;Sasako M;Mimori K

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由于转移性疾病的高频率,被诊断患有胃癌的个体的预后仍然很差。响应于肿瘤源性分泌因子,骨髓产生适合转移发展的微环境。然而,它在很大程度上是未知的分泌因子在骨髓中与胃癌患者的转移性疾病的存在。采用基因芯片技术检测胃癌转移患者骨髓中的分泌因子,并采用定量PCR技术检测355例骨髓、295例外周血和144例原发灶标本中的mRNA表达水平。本研究利用DNA微阵列分析技术,鉴定了骨形态发生蛋白8B(BMP 8B)作为一种与人胃癌转移相关的骨髓分泌型信号分子。355例胃癌患者骨髓中BMP 8B的表达水平随肿瘤转移而增高。骨髓和外周血中BMP 8B mRNA表达之间存在显著相关性。骨髓BMP 8B高表达与胃癌的弥漫型(P=0.009)、淋巴结转移(P= 0.009)、肝转移(P=0.044)和腹膜转移(P<0.001)有关。多因素分析显示BMP 8B mRNA表达是胃癌的独立预后因素之一[风险比(HR),2.066; 95%CI,1.132-3.772]。这项研究表明,BMP 8B是一种以前未知的癌症进展分泌因子,有可能用作预后生物标志物。本研究可能提供了一个新的机制,胃癌细胞的传播。
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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发表时间: 2011-02-15
影响因子: 8.8
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发表时间: 2011-10-30
期刊: Nature medicine
影响因子: 82.9
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