Aberrant upregulation of 14-3-3ơ expression serves as an inferior prognostic biomarker for gastric cancer.
Aberrant upregulation of 14-3-3ơ expression serves as an inferior prognostic biomarker for gastric cancer.
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14-3-3o 表达的异常上调是胃癌的较差预后生物标志物。
DOI：
10.1186/1471-2407-11-397
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发表时间：
2011-09-20
期刊：
影响因子：
3.8
通讯作者：
Liu Q
中科院分区：
文献类型：
--
作者：
Zhou WH;Tang F;Xu J;Wu X;Feng ZY;Li HG;Lin DJ;Shao CK;Liu Q
14-3- 3 β是一种细胞内磷酸丝氨酸结合蛋白，被认为与肿瘤发生有关。然而，14-3- 3 β在人类肿瘤中的表达动态及其临床病理学/预后意义仍存在争议。采用免疫组化和Western blot方法检测14-3- 3 β在胃癌组织及癌旁正常胃黏膜组织中的表达。采用受试者工作特征（ROC）曲线分析来确定训练集（n = 66）中14-3- 3 β表达的截止分数。为了验证，在测试集（n = 86）和总体患者（n = 152）中，对ROC衍生的截止分数进行14-3- 3 β表达与患者结果和临床特征的关联的分析。14-3- 3 β在胃癌组织中的表达频率和表达水平均显著高于正常胃粘膜组织。相关性分析显示14-3- 3 β在胃癌组织中的高表达与临床分期及肿瘤浸润深度显著相关。此外，在测试集和总体患者中，Kaplan-Meier分析显示，14-3- 3 β表达升高预测总生存期（OS）和无进展生存期（PFS）较差。重要的是，14-3- 3 β的高表达也与III期和IV期胃癌患者的生存时间缩短相关。多变量分析显示14-3- 3表达是胃癌的独立预后参数。提示14-3- 3 β在胃癌中的高表达可能在胃癌的发生、发展过程中起重要作用，并可作为胃癌预后不良的独立分子标志物。因此，14-3- 3 β的过表达鉴定了处于高风险的患者，并且是该肿瘤的新的治疗分子靶点。
14-3-3ơ is an intracellular, phosphoserine binding protein and proposed to be involved in tumorigenesis. However, the expression dynamics of 14-3-3ơ and its clinicopathological/prognostic significance in human tumors are still controversial. The method of immunohistochemistry (IHC) and Western blot were utilized to examine the protein expression of 14-3-3ơ in gastric cancer and paired normal adjacent gastric mucosal tissues. Receive operating characteristic (ROC) curve analysis was employed to determine a cutoff score for 14-3-3ơ expression in a training set (n = 66). For validation, the ROC-derived cutoff score was subjected to analysis of the association of 14-3-3ơ expression with patient outcome and clinical characteristics in a testing set (n = 86) and overall patients (n = 152). The expression frequency and expression levels of 14-3-3ơ were significantly higher in gastric cancer than in normal gastric mucosal tissues. Correlation analysis demonstrated that high expression of 14-3-3ơ in gastric cancer was significantly correlated with clinical stage and tumor invasion. Furthermore, in the testing set and overall patients, Kaplan-Meier analysis showed that elevated 14-3-3ơ expression predicted poorer overall survival (OS) and progression-free survival (PFS). Importantly, high 14-3-3ơ expression was also associated with shortened survival time in stage III and stage IV gastric cancer patients. Multivariate analyses revealed that 14-3-3ơ expression was an independent prognostic parameter in gastric cancer. These findings provide evidence that high expression of 14-3-3ơ may be important in the tumor progression and servers as an independent molecular marker for poor prognosis of gastric cancer. Thus, overexpression of 14-3-3ơ identifies patients at high risk and is a novel therapeutic molecular target for this tumor.
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