Masuda Takanobu, Nakashima Yuichiro, Ando Koji, Yoshinaga Keiji, Saeki Hiroshi, Oki Eiji, Morita Masaru, Oda Yoshinao, Maehara Yoshihiko
Department of Surgery and Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Department of Surgery and Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Anticancer Res. 2014 Nov;34(11):6397-403.
The CXCL12/CXCR4 axis plays a pivotal role in cancer progression and metastases in various epithelial cancer cells. The aim of the present study was to evaluate the localization and correlation between CXCL12/CXCR4 expression and clinicopathological features in gastric cancers.
This study included 111 Japanese patients with primary gastric cancers, which invade submucosa or more, all of whom underwent gastrectomy between 1992 and 1996. Immunohistochemical analysis was performed.
A significant correlation was found in the immunoreactivity of nuclear CXCR4 and poor differentiation (p=0.0026), infiltrated pattern (p<0.0001), larger size (p<0.0001), advanced stage (p=0.0342) and reduced 5-year survival rate (30% vs. 61%, p=0.0012). Multivariate analysis revealed that high nuclear CXCR4 immunoreactivity (RR: 3.077, p=0.0329) retained its strength as an independent prognostic factor for overall survival.
High immunoreactivity of nuclear CXCR4 in gastric cancer suggests that CXCL12 binds to its unique receptor CXCR4 at the membrane, translocates to the nucleus and then becomes more invasive, and thus can be considered a prognostic factor.
CXCL12/CXCR4轴在多种上皮癌细胞的癌症进展和转移中起关键作用。本研究的目的是评估CXCL12/CXCR4表达在胃癌中的定位及其与临床病理特征的相关性。
本研究纳入了111例日本原发性胃癌患者，这些患者的肿瘤侵犯至黏膜下层或更深层，所有患者均在1992年至1996年间接受了胃切除术。进行了免疫组织化学分析。
发现核CXCR4免疫反应性与低分化（p = 0.0026）、浸润模式（p < 0.0001）、更大尺寸（p < 0.0001）、晚期（p = 0.0342）以及5年生存率降低（30%对61%，p = 0.0012）之间存在显著相关性。多变量分析显示，高核CXCR4免疫反应性（相对风险：3.077，p = 0.0329）作为总生存的独立预后因素仍具有显著性。
胃癌中核CXCR4的高免疫反应性表明，CXCL12在细胞膜上与其独特受体CXCR4结合，转运至细胞核，进而变得更具侵袭性，因此可被视为一个预后因素。
