Ectopic expression of MECA-79 as a novel prognostic indicator in gastric cancer
Ectopic expression of MECA-79 as a novel prognostic indicator in gastric cancer
复制标题
DOI：
10.1111/j.1349-7006.2011.01895.x
复制
发表时间：
2011-05-01
期刊：
影响因子：
5.7
通讯作者：
Takenoshita, Seiichi
中科院分区：
文献类型：
--
作者：
Okayama, Hirokazu;Kumamoto, Kensuke;Takenoshita, Seiichi
这项研究的目的是阐明一种独特的碳水化合物决定簇MECA-79在胃癌标本和细胞中的临床意义。免疫组织化学分析显示，225例中62例(27.6%)MECA-79阳性。MecA-79的表达与肿瘤的侵袭深度、静脉侵犯、TNM分期和远处转移有关。生存分析显示，MECA-79表达阳性的患者预后较差。COX比例风险模型的多变量分析表明，MECA-79的表达是癌症特异性生存较差的独立因素。在11个胃癌细胞中，只有MKN7细胞表达MECA-79，MKN7细胞也表达GlcNAc6ST-2转录本。在MKN7细胞中，GlcNAc6ST-2被敲除后，MECA-79的表达显著降低，提示MECA-79的GlcNAc-硫化主要由GlcNAc6ST-2合成。此外，实时定量RT-PCR分析显示，癌组织中GlcNAc6ST-2的表达显著高于配对的正常粘膜。结论：MECA-79的表达可作为判断胃癌预后的有用指标。我们的结果也可能为MECA-79和GlcNAc6ST-2在癌症进展和转移中的生物学提供新的视角。(《癌症科学》2011；102：1088-1094)。
The aim of this study was to clarify the clinical implications of a unique carbohydrate determinant, MECA-79, in gastric cancer specimens and cells. Immunohistochemical analysis showed that 62 of 225 (27.6%) cases were defined as positive for MECA-79. MECA-79 expression was correlated with depth of invasion, venous invasion, TNM stage, and distant metastasis. In survival analyses, patients with MECA-79 expression had worse prognosis by the log-rank test. Multivariate analysis of the Cox proportional hazard model showed that MECA-79 expression was an independent factor of a worse cancer-specific survival. Among 11 gastric cancer cells, MECA-79 was observed in only MKN7 cells, which also expressed GlcNAc6ST-2 transcript. A knockdown of GlcNAc6ST-2 in MKN7 cells showed a markedly reduced expression of MECA-79, suggesting that GlcNAc-sulfation of MECA-79 is mainly synthesized by GlcNAc6ST-2. Furthermore, real-time RT-PCR analysis revealed that GlcNAc6ST-2 was significantly increased in cancer tissues compared with paired normal mucosa. In conclusion, the expression of MECA-79 could be a useful marker for the prognosis of gastric cancer. Our results might also provide novel perspectives on the biology of MECA-79 and GlcNAc6ST-2 in cancer progression and metastasis. (Cancer Sci 2011; 102: 1088-1094).