Upregulation of HOXA10 in gastric cancer with the intestinal mucin phenotype: reduction during tumor progression and favorable prognosis
Upregulation of HOXA10 in gastric cancer with the intestinal mucin phenotype: reduction during tumor progression and favorable prognosis
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DOI：
10.1093/carcin/bgs121
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发表时间：
2012-05-01
期刊：
影响因子：
4.7
通讯作者：
Yasui, Wataru
中科院分区：
文献类型：
--
作者：
Sentani, Kazuhiro;Oue, Naohide;Yasui, Wataru
胃癌（GC）是全世界最常见的恶性肿瘤之一。更好地了解胃癌发生过程中基因表达的变化可能会改善诊断、治疗和预防。在本研究中，我们通过比较微阵列的基因表达谱和基因表达的系列分析来筛选GC中上调的基因，并鉴定出HOXA10基因。本研究的目的是探讨 HOXA10 在 GC 中的意义。免疫组织化学分析显示，749例GC病例中有221例（30%）HOXA10呈阳性，而除肠化生病例外，HOXA10在非肿瘤性胃粘膜中几乎不表达。接下来，我们分析了HOXA10表达与临床病理特征的关系。 HOXA10表达与浸润深度呈显着负相关，并且在分化型GC中比在未分化型GC中更常见。 HOXA10 表达与具有肠道粘蛋白表型的 GC 相关，并与 CDX2 表达相关。此外，HOXA10表达阳性的患者预后明显好于阴性表达的患者。 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴化物和伤口愈合测定表明，通过短干扰RNA转染敲低GC细胞中的HOXA10，相对于阴性对照显着增加活力和运动性，表明HOXA10表达抑制细胞生长和运动。这些结果表明 HOXA10 的表达可能是具有肠道粘蛋白表型的 GC 的关键调节因子。
Gastric cancer (GC) is one of the most common malignancies worldwide. Better knowledge of the changes in gene expression that occur during gastric carcinogenesis may lead to improvements in diagnosis, treatment and prevention. In this study, we screened for genes upregulated in GC by comparing gene expression profiles from microarray and serial analysis of gene expression and identified the HOXA10 gene. The aim of the present study was to investigate the significance of HOXA10 in GC. Immunohistochemical analysis demonstrated that 221 (30%) of 749 GC cases were positive for HOXA10, whereas HOXA10 was scarcely expressed in non-neoplastic gastric mucosa except in the case of intestinal metaplasia. Next, we analyzed the relationship between HOXA10 expression and clinicopathological characteristics. HOXA10 expression showed a significant inverse correlation with the depth of invasion and was observed more frequently in the differentiated type of GC than in the undifferentiated type of GC. HOXA10 expression was associated with GC with the intestinal mucin phenotype and correlated with CDX2 expression. Furthermore, the prognosis of patients with positive HOXA10 expression was significantly better than in the negative expression cases. 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide and wound healing assay revealed that knockdown of HOXA10 in GC cells by short interfering RNA transfection significantly increased viability and motility relative to the negative control, indicating that HOXA10 expression inhibits cell growth and motility. These results suggest that expression of HOXA10 may be a key regulator for GC with the intestinal mucin phenotype.