The expression and clinical significance of HERC4 in breast cancer.

The expression and clinical significance of HERC4 in breast cancer.
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HERC4在乳腺癌中的表达及临床意义

DOI:
10.1186/1475-2867-13-113
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发表时间:
2013-11-14
影响因子:
5.8
通讯作者:
Ma WL
Ma WL
中科院分区:
医学2区
文献类型:
--
作者:
Zhou H;Shi R;Wei M;Zheng WL;Zhou JY;Ma WL

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背景越来越多的证据表明,泛素-蛋白酶体系统(UPS)在肿瘤发生中起着关键作用。HERC 4是最近鉴定的泛素连接酶。然而,HERC 4在肿瘤中的表达状况及其生物学功能尚不清楚。方法采用实时荧光定量PCR和Western blot方法检测HERC 4在乳腺癌细胞系和乳腺癌组织中的表达。为探讨HERC 4在乳腺癌中的临床病理意义,采用免疫组织化学方法对13例乳腺良性纤维腺瘤、15例乳腺导管内癌、120例乳腺浸润性导管癌组织芯片进行HERC 4的检测。采用受试者工作特征(ROC)分析确定HERC 4阳性表达的最佳临界值,当HERC 4阳性表达率大于60%时,肿瘤定义为“阳性”。ROC曲线分析显示,HERC 4在正常乳腺组织中阳性表达率为6.3%,在纤维腺瘤中阳性表达率为23.1%,在导管内癌中阳性表达率为40%,在浸润性导管癌中阳性表达率为55%。HERC 4的阳性表达与乳腺浸润性导管癌的pT、pN、临床分期及组织学分级呈正相关(p < 0.05)。
BackgroundIncreasing evidence suggest that ubiquitin-proteasome system (UPS) plays a key role in tumorigenesis. HERC4 is a recently identified ubiqutin ligase. However, the expression status and biological functions of HERC4 in cancers are not clearly.MethodsWe evaluated the HERC4 expression in breast cancer cell lines and breast tumor tissues by quantitative real-time PCR and western blot analysis. To investigate the clinicopathological significance of HERC4, immunohistochemistry analysis for HERC4 was performed on a tissue microarray including 13 benign fibroadenoma, 15 intraductal carcinoma, 120 histologically confirmed invasive ductal carcinoma. Receiver operating characteristic (ROC) analysis was applied to determine the optimal cut-off score for positive expression of HERC4, when HERC4 positive expression percentage was above 60%, tumor was defined as “positive”.ResultsHERC4 was up-regulated in breast cancer cell lines and breast tumor tissues compared to non-tumorigenic cell line and adjacent normal breast tissues. According to ROC analysis, HERC4 positive expression was detected in 1/16 (6.3%) of normal breast tissue, in 3/13 (23.1%) of fibroadenoma, in 6/15 (40%) of intraductal carcinoma and 66/120 (55%) of invasive ductal carcinoma. Positive expression of HERC4 was positively correlated with pT status, pN status, clinical stage and histological grade of patients with invasive ductal carcinoma (p < 0.05).ConclusionsOur findings suggest that HERC4 was a significant diagnostic marker for invasive ductal carcinoma of the breast.
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