人胃癌中58 kDa微球蛋白（MSP58）表达增加促进细胞增殖并与患者预后不良相关。

Increased Expression of 58-kDa Microspherule Protein (MSP58) in Human Gastric Cancer Promotes Cell Proliferation and Correlates with Poor Patient Survival.

作者信息

Cui Jianxin, Xi Hongqing, Cai Aizhen, Ma Liangang, Bian Shibo, Zhang Kecheng, Wei Bo, Chen Lin

出版信息

Clin Lab. 2016;62(6):993-1001. doi: 10.7754/clin.lab.2015.150828.

DOI:10.7754/clin.lab.2015.150828

PMID:27468560

Abstract

BACKGROUND

Gastric cancer (GC) is one of the most frequently occurring malignancies with poor prognosis because of its huge heterogeneity and limited available therapeutic options. The nucleolar 58-kDa microspherule protein (MSP58) is involved in a variety of cellular processes. Though MSP58 was identified as a candidate oncogene in many cancer types, it has both oncogenic and tumor suppressive properties. The oncogenic effect of MSP58 in GC is currently unclear. The present study identified MSP58 expression in GCs and investigated its role in tumor proliferation and patient survival.

METHODS

MSP58 expression in GCs was identified using western blotting and immunochemistry methods and correlations with clinicopathological features. Patient survival was calculated by multivariate survival analysis. Small interference RNA transfection, CCK8, and clonogenic assays were performed to investigate the roles of MSP58 in cell proliferation.

RESULTS

MSP58 was highly expressed in MGC803, BGC823, and NCI-N87 cell lines compared with normal gastric mucosa cells. The study thus provided evidence that knockdown of MSP58 expression significantly suppressed cell proliferation and colony-forming ability. Immunohistochemical analysis showed MSP58 was highly expressed in 51.5% of GC tissues and in 11.9% of normal corresponding mucosal tissues. Significant positive correlations between MSP58 expression and differentiation grade, depth of invasion, and pathological tumor node metastasis (TNM) stage was further identified. The overall 5-year survival rate for the MSP58-positive group was lower than that of the MSP58-negative group. Depth of invasion, lymph node metastasis, and MSP58 expression were found to be independent prognostic factors.

CONCLUSIONS

These findings suggested that MSP58 plays an important role in tumorigenesis and progression and may help predict the prognosis of GC patients.

摘要

背景

胃癌（GC）是最常见的恶性肿瘤之一，由于其高度异质性和有限的可用治疗选择，预后较差。核仁58 kDa微球蛋白（MSP58）参与多种细胞过程。尽管MSP58在许多癌症类型中被鉴定为候选癌基因，但它具有致癌和肿瘤抑制特性。MSP58在GC中的致癌作用目前尚不清楚。本研究确定了MSP58在GC中的表达，并研究了其在肿瘤增殖和患者生存中的作用。

方法

采用蛋白质免疫印迹法和免疫组化方法鉴定GC中MSP58的表达，并分析其与临床病理特征的相关性。通过多因素生存分析计算患者生存率。进行小干扰RNA转染、CCK8和克隆形成试验，以研究MSP58在细胞增殖中的作用。

结果

与正常胃黏膜细胞相比，MSP58在MGC803、BGC823和NCI-N87细胞系中高表达。该研究因此提供了证据，即敲低MSP58表达可显著抑制细胞增殖和集落形成能力。免疫组化分析显示，MSP58在51.5%的GC组织和11.9%的相应正常黏膜组织中高表达。进一步确定了MSP58表达与分化程度、浸润深度和病理肿瘤淋巴结转移（TNM）分期之间存在显著正相关。MSP58阳性组的总体5年生存率低于MSP58阴性组。浸润深度、淋巴结转移和MSP58表达被发现是独立的预后因素。