Overexpression of CLIC1 in human gastric carcinoma and its clinicopathological significance

Overexpression of CLIC1 in human gastric carcinoma and its clinicopathological significance
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DOI:
10.1002/pmic.200600663
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发表时间:
2007-01-01
期刊:
影响因子:
3.4
通讯作者:
Lin, Kwang-Huei
Lin, Kwang-Huei
中科院分区:
生物学3区
文献类型:
--
作者:
Chen, Chi-De;Wang, Chia-Siu;Lin, Kwang-Huei

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胃癌是全球第二大常见癌症,也是台湾第五大癌症相关死亡原因。生物标志物的鉴定对于提高患者生存率至关重要。采用双向电泳结合MALDI-TOF-MS鉴定了50个异常表达的蛋白质,并根据其功能进行了分组。用实时定量RT-PCR、Western blot和免疫组化分析证实蛋白质的过表达。这些异常表达蛋白的临床病理相关性和预后意义进行了评估,以确定新的胃癌生物标志物。在这项研究中,氯细胞内通道1(CLIC 1)的表达在67.9%的胃患者中显著上调,并被选择用于进一步研究。CLIC 1在肿瘤组织中的表达与癌旁粘膜相比增加了1.95倍(范围,0.01-6.19倍)。CLIC 1的高表达与淋巴结转移、淋巴管浸润、神经浸润和病理分期密切相关。此外,CLIC 1低表达组的5年生存率(n = 28; < 1.72倍)高于CLIC 1高表达组(n = 28; >= 72倍)(对数秩,p = 0.0300)。实验结果表明,CLIC 1的过度表达是胃癌的一个潜在的预后指标。
Gastric cancer is the second most common cancer worldwide and the fifth leading cause of cancer-related death in Taiwan. Identification of biomarkers is essential to improve patient survival. Fifty aberrantly expressed proteins were identified using 2-DE combined with MALDI TOF MS and were grouped based on their function. The overexpression of proteins was confirmed using real-time quantitative RT-PCR, Western blot, and immumohistochemical analysis. The clinicopathological correlations and prognostic significance of these aberrantly expressed proteins were evaluated to determine the novel gastric cancer biomarkers. In this study, expression of chloride intracellular channel 1 (CLIC1) is significantly up-regulated in 67.9% of gastric patients and was selected for further study. The CLIC1 expression in tumor tissues was increased by 1.95-fold (range, 0.01-6.19-fold) compared with that expressed by adjacent noncancerous mucosa. Elevated CLIC1 expression was strongly correlated with lymph node metastasis, lymphatic invasion, perineural invasion, and pathological staging. Additionally, the 5-year survival rate for the low CLIC1 expression group (n = 28; < 1.72-fold) was higher than that for the high CLIC1 expression group (n = 28; >= 72-fold) (log rank, p = 0.0300). Experimental results indicate that over-expression of CLIC1 is a potential prognostic marker for gastric cancer.