Identification and validation that up-expression of HOXA13 is a novel independent prognostic marker of a worse outcome in gastric cancer based on immunohistochemistry
Identification and validation that up-expression of HOXA13 is a novel independent prognostic marker of a worse outcome in gastric cancer based on immunohistochemistry
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基于免疫组织化学鉴定和验证 HOXA13 的上表达是胃癌预后较差的新型独立预后标志物
DOI：
10.1007/s12032-013-0564-1
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发表时间：
2013-06-01
期刊：
影响因子：
3.4
通讯作者：
Zhou, Chong-zhi
中科院分区：
文献类型：
--
作者：
Han, Yang;Tu, Wei-wei;Zhou, Chong-zhi
同源盒（HOX）基因家族被认为是胚胎发生和肿瘤发生之间密切关系的经典例子。然而，对于HOX基因家族与胃癌发生的关系知之甚少。在此，我们通过cDNA微阵列筛选HOX基因家族在胃癌中的表达并探讨它们之间的关系。我们在胃癌中发现了几个差异表达的HOX基因，特别是HOXA10（11/12）和HOXA13（11/12）在癌组织中的表达显着较高。此外，我们基于免疫组织化学和统计分析验证了 HOXA13 作为胃癌的新型预后标志物。与相应的非癌粘膜相比，癌组织中 HOXA13 的表达显着上调（P < 0.001）。 HOXA13的上表达与T分期（P = 0.002）、M分期（P = 0.024）、晚期UICC分期（P < 0.001）、组织学分化（P = 0.005）和复发（P = 0.001）显着相关。 HOXA13表达阳性患者的总生存率（OS）和无病生存率（DFS）明显低于HOXA13表达阴性患者（HR 3.331，95% CI 1.722-6.442，P < 0.001；HR 3.289，95 % CI 1.703-6.351，P < 0.001）。单变量和多变量 Cox 分析证实 HOXA13 可以作为 DFS 和 OS 的重要独立预后因素。因此，我们的研究结果表明，多个HOX基因可能与胃肿瘤的发生过程密切相关。此外，HOXA13的上表达可能与胃癌的高度侵袭性表型相关。 HOXA13是一个重要的独立预后因素，可以作为胃癌诊断和预后的假定生物标志物。
Homeobox (HOX) gene family is known to be classic examples of the intimate relationship between embryogenesis and tumorigenesis. However, less is known about the involvement of HOX gene family with gastric cancerogenesis. Here, we screened the expression of HOX gene family in gastric cancers and explored the relationships between them by cDNA microarray. We found several differentially expressed HOX genes in gastric cancers, especially HOXA10 (11/12) and HOXA13 (11/12) with significantly higher expression in the cancerous tissues. Furthermore, we validated HOXA13 as a novel prognostic marker in gastric cancer based on immunohistochemistry and statistical analysis. HOXA13 expression was significantly up-regulated in cancerous tissues compared with the corresponding non-cancerous mucosa (P < 0.001). Up-expression of HOXA13 was significantly correlated with T stage (P = 0.002), M stage (P = 0.024), advanced UICC stage (P < 0.001), histological differentiation (P = 0.005), and relapse (P = 0.001). Patients with positive HOXA13 expression had a obviously lower overall survival (OS) and disease-free survival (DFS) rate than patients with negative HOXA13 expression (HR 3.331, 95 % CI 1.722-6.442, P < 0.001; HR 3.289, 95 % CI 1.703-6.351, P < 0.001, respectively). Univariate and multivariate Cox analysis confirmed that HOXA13 could serve as a significant independent prognostic factor for DFS and OS. Therefore, our results indicated that several HOX genes might be closely involved in the process of the gastric tumorigenesis. Furthermore, up-expression of HOXA13 might be associated with highly aggressive phenotype of gastric cancer. HOXA13 was a significant independent prognostic factor and could serve as a putative biomarker for diagnosis and prognosis of gastric cancer.