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整合素α5促进肿瘤进展,是食管鳞状细胞癌中一个独立的不良预后因素。

Integrin α5 promotes tumor progression and is an independent unfavorable prognostic factor in esophageal squamous cell carcinoma.

作者信息

Xie Jian-Jun, Guo Jin-Cheng, Wu Zhi-Yong, Xu Xiu-E, Wu Jian-Yi, Chen Bo, Ran Li-Qiang, Liao Lian-Di, Li En-Min, Xu Li-Yan

机构信息

Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Medical College of Shantou University, Shantou 515041, PR China; Department of Biochemistry and Molecular Biology, Medical College of Shantou University, Shantou 515041, PR China.

Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Medical College of Shantou University, Shantou 515041, PR China; Department of Biochemistry and Molecular Biology, Medical College of Shantou University, Shantou 515041, PR China.

出版信息

Hum Pathol. 2016 Feb;48:69-75. doi: 10.1016/j.humpath.2015.09.029. Epub 2015 Oct 22.

Abstract

The integrin family plays a major role in complex biological events such as differentiation, development, wound healing, and the altered adhesive and invasive properties of tumor cells. The expression and function of integrin α5 in esophageal squamous cell carcinoma (ESCC) are not clear. Here, by using tissue microarrays and immunohistochemical method, integrin α5 expression was retrospectively evaluated in 147 samples of human ESCC. Results showed that expression of integrin α5 was heterogeneous and varied from negative to intense expression in a membrane and cytoplasmic distribution manner. High expression of integrin α5 was significantly correlated with lymph node metastasis (P = .042) and tumor size (P = .042). Kaplan-Meier analysis revealed that high expression of integrin α5 was related to poor overall survival of ESCC patients (P = .018). Multivariate analysis suggested that integrin α5 expression status was an independent prognostic factor for ESCC (P = .003). Moreover, integrin α5 expression was associated with the survival of patients with lymph node metastasis (P = .020), but did not influence the survival of patients without lymph node metastasis. Finally, we found that RNAi-mediated knockdown of integrin α5 led to decreased growth, migration, and invasion of ESCC cells. Combined, integrin α5 might play important roles in the progression of ESCC. Integrin α5 is a novel biomarker to predict the prognosis of ESCC patients.

摘要

整合素家族在诸如分化、发育、伤口愈合以及肿瘤细胞黏附性和侵袭性改变等复杂生物学事件中发挥着重要作用。整合素α5在食管鳞状细胞癌(ESCC)中的表达及功能尚不清楚。在此,通过组织芯片和免疫组化方法,对147例人ESCC样本进行回顾性评估整合素α5的表达。结果显示,整合素α5的表达具有异质性,以膜和细胞质分布的方式从阴性到强阳性表达不等。整合素α5的高表达与淋巴结转移(P = 0.042)和肿瘤大小(P = 0.042)显著相关。Kaplan-Meier分析显示,整合素α5的高表达与ESCC患者的总体生存率差有关(P = 0.018)。多因素分析表明,整合素α5的表达状态是ESCC的独立预后因素(P = 0.003)。此外,整合素α5的表达与有淋巴结转移患者的生存率相关(P = 0.020),但不影响无淋巴结转移患者的生存率。最后,我们发现RNAi介导的整合素α5敲低导致ESCC细胞的生长、迁移和侵袭能力下降。综合来看,整合素α5可能在ESCC的进展中起重要作用。整合素α5是预测ESCC患者预后的一种新型生物标志物。

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