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Cyr61/CCN1过表达诱导上皮-间质转化,导致喉肿瘤侵袭、转移及预后不良。

Cyr61/CCN1 overexpression induces epithelial-mesenchymal transition leading to laryngeal tumor invasion and metastasis and poor prognosis.

作者信息

Liu Ying, Zhou Yan-Dong, Xiao Yu-Li, Li Ming-Hua, Wang Yu, Kan Xuan, Li Qiu-Ying, Lu Jian-Guang, Jin De-Jun

机构信息

Department of Otolaryngology/Head and Neck Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China E-mail :

出版信息

Asian Pac J Cancer Prev. 2015;16(7):2659-64. doi: 10.7314/apjcp.2015.16.7.2659.

DOI:10.7314/apjcp.2015.16.7.2659
PMID:25854342
Abstract

BACKGROUND

To examine the expression of cysteine-rich 61 (Cyr61/CCN1) protein in laryngeal squamous- cell carcinoma (LSCC) tissues, and its relationship with the tumor epithelial-mesenchymal transition (EMT), invasion, metastasis, and prognosis.

MATERIALS AND METHODS

Immunohistochemistry was used to detect the expressions of Cyr61, Vimentin (Vim), and E-cadherin (E-cad) in 88 cases of LSCC tissues and 30 cases of tumor-adjacent normal tissues. Vim and E-cad were used as mesenchymal and epithelial markers, respectively, to determine the relationship between Cyr61 expression and the EMT of LSCC cells. In addition, clinical and histopathological data were combined to analyze the relationship between the positive-expression rates of Cyr61, Vim and E-cad and LSCC invasion, metastasis and prognosis.

RESULTS

In LSCC tissues, Vim expression rate was significantly higher than that of the tumor-adjacent tissues, whereas E-cad expression rate was significantly lower than that of the tumor-adjacent tissues. The Vim expression rate was significantly higher in stages T3 and T4 than in stages T1 and T2 LSCC tissues, whereas E-cad expression rate was significantly lower in stages T3 and T4 than in stages T1 and T2 LSCC tissues. Compared to the group without lymph node metastasis, the Vim expression rate was significantly higher and the E-cad expression rate was significantly lower in the group with lymph node metastasis. The expression rate of Cyr61 was significantly higher in LSCC tissues than in the tumor-adjacent normal tissues. In addition, the Cyr61 expression rate was higher in stages T3 and T4 than in stages T1 and T2 LSCC, and higher in the group with lymph node metastasis than in the group without lymph node metastasis. The Vim expression rate was significantly higher in the Cyr61 positive group than in the Cyr61 negative group, whereas the E-cad expression rate was significantly higher in the Cyr61 negative group than in the Cyr61 positive group. Survival analysis indicated that survival rates of Cyr61 positive, Vim positive and E-cad negative groups were significantly lower than that of Cyr61 negative, Vim negative and E-cad positive groups, respectively.

CONCLUSIONS

Cyr61 expression is closely associated with LSCC invasion and lymph node metastasis. Overexpression of Cyr61 may induce EMT and therefore leads to LSCC invasion and metastasis and poor prognosis. Cyr61 may become a new maker for clinical prediction of LSCC invasion and metastasis and a new target for LSCC treatment.

摘要

背景

检测富含半胱氨酸的61蛋白(Cyr61/CCN1)在喉鳞状细胞癌(LSCC)组织中的表达情况,并探讨其与肿瘤上皮-间质转化(EMT)、侵袭、转移及预后的关系。

材料与方法

采用免疫组织化学法检测88例LSCC组织及30例癌旁正常组织中Cyr61、波形蛋白(Vim)和E-钙黏蛋白(E-cad)的表达。分别以Vim和E-cad作为间质和上皮标志物,确定Cyr61表达与LSCC细胞EMT的关系。此外,结合临床和组织病理学数据,分析Cyr61、Vim和E-cad阳性表达率与LSCC侵袭、转移及预后的关系。

结果

在LSCC组织中,Vim表达率显著高于癌旁组织,而E-cad表达率显著低于癌旁组织。T3和T4期LSCC组织中Vim表达率显著高于T1和T2期,而T3和T4期E-cad表达率显著低于T1和T2期。与无淋巴结转移组相比,有淋巴结转移组Vim表达率显著升高,E-cad表达率显著降低。LSCC组织中Cyr61表达率显著高于癌旁正常组织。此外,T3和T4期LSCC中Cyr61表达率高于T1和T2期,有淋巴结转移组高于无淋巴结转移组。Cyr61阳性组Vim表达率显著高于Cyr61阴性组,而Cyr61阴性组E-cad表达率显著高于Cyr61阳性组。生存分析表明,Cyr61阳性、Vim阳性和E-cad阴性组的生存率分别显著低于Cyr61阴性、Vim阴性和E-cad阳性组。

结论

Cyr61表达与LSCC侵袭及淋巴结转移密切相关。Cyr61过表达可能诱导EMT,进而导致LSCC侵袭、转移及预后不良。Cyr61可能成为临床预测LSCC侵袭和转移的新标志物及LSCC治疗的新靶点。

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