WWOX的异常表达及其与癌症干细胞生物标志物表达的关联。

Aberrant expression of WWOX and its association with cancer stem cell biomarker expression.

作者信息

Zhai Yunzhi, Han Yajuan, Han Zhengquan

机构信息

Department of Medical Oncology, Pathology, The First Affiliated Hospital of Bengbu Medical College Anhui, China.

出版信息

Int J Clin Exp Pathol. 2020 May 1;13(5):1176-1184. eCollection 2020.

PMID:32509092

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7270669/

Abstract

BACKGROUND

Nanog and CD133 are biomarkers of cancer stem cells (CSCs) that regulate cancer progression. The WW domain-containing oxidoreductase (WWOX) is a tumor suppressor protein that can inhibit tumor cell proliferation. The purpose of this study was to investigate the expression and clinical significance of Nanog, CD133, and WWOX in infiltrating breast cancer (IBC).

METHODS

Expressions of Nanog, CD133, and WWOX in 204 IBC specimens and their corresponding control specimens were detected by immunohistochemistry. Patients' clinicopathologic and follow-up data were also collected.

RESULTS

The rates of positive expression of Nanog and CD133 were significantly higher in IBC specimens than in control specimens, and their expression was positively associated with tumor size, grade, and tumor stages, lymph node metastasis (LNM), and tumor-node-metastasis (TNM) stage. The rate of positive expression of WWOX was significantly lower in IBC specimens than in control specimens, and its expression was inversely associated with tumor size, grade, and tumor stages, LNM, and TNM stage. Patients whose specimens expressed Nanog, CD133, or HER2 had a reduced overall survival (OS) when compared with patients not expressing these proteins. However, patients whose specimens expressed WWOX, ER, or PR had an increased OS when compared with patients who did not show expression. Multivariate analysis demonstrated that expression of Nanog, CD133, WWOX, ER, and HER2, and the TNM stage were independent prognostic factors for IBC patients.

CONCLUSIONS

Therefore, Nanog, CD133, and WWOX should be considered as promising prognostic factors and therapeutic targets in IBC.

摘要

背景

Nanog和CD133是调节癌症进展的癌症干细胞（CSCs）生物标志物。含WW结构域的氧化还原酶（WWOX）是一种肿瘤抑制蛋白，可抑制肿瘤细胞增殖。本研究旨在探讨Nanog、CD133和WWOX在浸润性乳腺癌（IBC）中的表达及其临床意义。

方法

采用免疫组织化学法检测204例IBC标本及其相应对照标本中Nanog、CD133和WWOX的表达。同时收集患者的临床病理及随访资料。

结果

IBC标本中Nanog和CD133的阳性表达率显著高于对照标本，且其表达与肿瘤大小、分级、肿瘤分期、淋巴结转移（LNM）及肿瘤-淋巴结-转移（TNM）分期呈正相关。IBC标本中WWOX的阳性表达率显著低于对照标本，且其表达与肿瘤大小、分级、肿瘤分期、LNM及TNM分期呈负相关。与未表达这些蛋白的患者相比，标本表达Nanog、CD133或HER2的患者总生存期（OS）缩短。然而，与未表达WWOX、雌激素受体（ER）或孕激素受体（PR）的患者相比，标本表达这些蛋白的患者OS延长。多因素分析表明，Nanog、CD133、WWOX、ER、HER2的表达及TNM分期是IBC患者的独立预后因素。