Sineoculis homeobox homolog 1 protein overexpression as an independent biomarker for pancreatic ductal adenocarcinoma

Sineoculis homeobox homolog 1 protein overexpression as an independent biomarker for pancreatic ductal adenocarcinoma
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Sineoculis 同源盒同源物 1 蛋白过度表达作为胰腺导管腺癌的独立生物标志物。

DOI:
10.1016/j.yexmp.2013.11.003
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发表时间:
2014-02-01
影响因子:
3.6
通讯作者:
Lin, Zhenhua
Lin, Zhenhua
中科院分区:
医学3区
文献类型:
--
作者:
Jin, Aihua;Xu, Yunjie;Lin, Zhenhua

文献摘要

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Sineoculis Homeobox Homolog 1(SIX1)是六基因家族中的一员。它在来源于在胚胎发育过程中发挥基础作用的组织的癌症中高度表达。最近的研究表明,SIX1的不适当表达既可以启动肿瘤的发生,又可以促进转移。为探讨SIX1在胰腺导管腺癌(PDAC)中的表达及其临床病理意义,进一步探讨SIX1在PDAC中的作用,采用免疫组织化学方法检测103例PDAC组织和45例正常胰腺组织中SIX1蛋白的表达。免疫荧光染色检测SIX1蛋白在PANC-1癌细胞中的定位。SIX1过度表达与胰腺癌临床病理特征的相关性采用卡方检验,生存曲线差异分析采用对数等级检验,多因素生存分析采用COX比例风险回归模型。免疫组织化学结果显示,SIX1蛋白在PDAC中主要表现为胞浆/核周染色。胰腺癌组织中SIX1蛋白表达强阳性率为60.2%(62/103),明显高于正常胰腺组织的6.7%(3/45)。SIX1过表达与肿瘤大小、TNM分期、淋巴结转移和肿瘤分化程度呈正相关(P<0.001)。SIX1高表达影响PDAC中C_1、G_2期、I~II期和III~IV期的总生存率,高表达组总生存率显著低于低表达组。综上所述,SIX1是PDAC中一个重要的独立预后因素。SIX1的过度表达可能与PDAC有关,可能成为PDAC早期诊断和预后评估的潜在生物标志物。(C)2013 Elsevier Inc.保留所有权利。
Sineoculis homeobox homolog 1 (SIX1) is a member of the SIX gene family. It is highly expressed in cancers derived from tissues that play a fundamental role during embryogenesis. Recent studies suggest that inappropriate expression of SIX1 can both initiate tumorigenesis and promote metastasis. To investigate the clinicopathological significance of SIX1 expression in pancreatic ductal adenocarcinoma (PDAC), and to further identify its role as a potential biomarker and therapeutic target in PDAC, 103 PDAC tissue samples and 45 normal pancreatic tissue samples were immunohistochemically stained for SIX1 protein. The localization of SIX1 protein was detected in Panc-1 cancer cells using immunofluorescence staining. Correlations between SIX1 overexpression and the clinicopathological features of pancreatic cancer were evaluated using Chi-square (x2) tests, differences in survival curves were analyzed using log-rank tests, and multivariate survival analysis was performed using the Cox proportional hazard regression model. In results, SIX1 protein showed mainly cytoplasmic/perinuclear staining pattern in PDAC with immunohistochemistry. The strongly positive rate of SIX1 protein was 60.2% (62/103) in PDAC, which was significantly higher than normal pancreatic tissue (6.7%, 3/45). SIX1 overexpression was positively correlated with tumor size, TNM stage, lymph node metastasis, and grade of PDAC (P < 0.001). SIX1 high expression levels influenced overall survival rates in C1, G2, stage I-II and stage III-IV groups of PDAC; and high expression levels had significantly lower overall survival rates than SIX1 low expression levels. In conclusion, SIX1 emerged as a significant independent prognostic factor in PDAC. SIX1 overexpression appears to be associated with PDAC, and may be a potential biomarker for early diagnosis and prognostic evaluation of PDAC. (C) 2013 Elsevier Inc All rights reserved.