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热休克蛋白47(HSP47)在食管鳞状细胞癌中的过表达:临床意义及功能分析

Overexpression of HSP47 in esophageal squamous cell carcinoma: clinical implications and functional analysis.

作者信息

Lee H W, Kwon J, Kang M C, Noh M-K, Koh J S, Kim J H, Park J H

机构信息

Department of Thoracic Surgery, Korea Cancer Center Hospital, Seoul, Korea.

Department of Translational Research, Korea Cancer Center Hospital, Seoul, Korea.

出版信息

Dis Esophagus. 2016 Oct;29(7):848-855. doi: 10.1111/dote.12359. Epub 2015 May 8.

Abstract

Several biomarkers of esophageal squamous cell carcinoma (ESCC) have been explored to improve the prognosis of this disease. One of these, the 47-kDa heat shock protein (HSP47), has been screened as a potential biomarker by genomic profiling and is known to be overexpressed in some malignant diseases. In this study, we explored the role and evaluated the prognostic value of HSP47 expression in ESCC. The function of this protein was analyzed by assaying proliferation, wound healing, and colony formation in an HSP47-knockdown ESCC line. The prognostic implication of HSP47 expression was analyzed by immunohistochemical staining in 157 surgical specimens. HSP47 expression level and other clinical variables were analyzed using multivariate Cox proportional hazards models. Silencing of the HSP47 gene in the ESCC cell line inhibited cell proliferation and colony formation. HSP47 was highly expressed in ESCC tissue samples, compared with normal esophageal tissues. The level of immunohistochemical staining of HSP47 and pathologic stage were significantly correlated with overall and recurrence-free survival, as shown by multivariate analysis (P = 0.014 and 0.044, respectively). We found that overexpression of HSP47 is associated with poor prognosis in patients with ESCC and that this is consistent with the function of HSP47 in terms of increased cell proliferation and colony formation. These results suggest that HSP47 is a potential prognostic biomarker for ESCC and merits further research for novel diagnostic and therapeutic applications.

摘要

为改善食管鳞状细胞癌(ESCC)的预后,人们探索了多种生物标志物。其中之一,47-kDa热休克蛋白(HSP47),已通过基因组分析被筛选为潜在生物标志物,且已知在某些恶性疾病中过表达。在本研究中,我们探讨了HSP47表达在ESCC中的作用并评估了其预后价值。通过检测HSP47敲低的ESCC细胞系中的增殖、伤口愈合和集落形成来分析该蛋白的功能。通过对157例手术标本进行免疫组织化学染色来分析HSP47表达的预后意义。使用多变量Cox比例风险模型分析HSP47表达水平和其他临床变量。ESCC细胞系中HSP47基因的沉默抑制了细胞增殖和集落形成。与正常食管组织相比,HSP47在ESCC组织样本中高表达。多变量分析显示,HSP47免疫组织化学染色水平和病理分期与总生存期和无复发生存期显著相关(分别为P = 0.014和0.044)。我们发现HSP47的过表达与ESCC患者的不良预后相关,并且这在HSP47促进细胞增殖和集落形成的功能方面是一致的。这些结果表明,HSP47是ESCC的潜在预后生物标志物,值得进一步研究以用于新的诊断和治疗应用。

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