Chen Chi-De, Wang Chia-Siu, Huang Ya-Hui, Chien Kun-Yi, Liang Ying, Chen Wei-Jan, Lin Kwang-Huei
Department of Biochemistry, Chang Gung University, Taoyuan, Taiwan, Republic of China.
Proteomics. 2007 Jan;7(1):155-67. doi: 10.1002/pmic.200600663.
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 immunohistochemical 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; >or=1.72-fold) (log rank, p = 0.0300). Experimental results indicate that overexpression of CLIC1 is a potential prognostic marker for gastric cancer.
胃癌是全球第二大常见癌症，在台湾是癌症相关死亡的第五大主要原因。生物标志物的鉴定对于提高患者生存率至关重要。使用二维电泳结合基质辅助激光解吸电离飞行时间质谱鉴定出50种异常表达的蛋白质，并根据其功能进行分组。通过实时定量逆转录聚合酶链反应、蛋白质印迹法和免疫组织化学分析证实了蛋白质的过表达。评估这些异常表达蛋白质的临床病理相关性和预后意义，以确定新的胃癌生物标志物。在本研究中，67.9%的胃癌患者中氯化物细胞内通道1（CLIC1）的表达显著上调，并被选择进行进一步研究。与相邻非癌黏膜相比，肿瘤组织中CLIC1的表达增加了1.95倍（范围为0.01 - 6.19倍）。CLIC1表达升高与淋巴结转移、淋巴管浸润、神经周围浸润和病理分期密切相关。此外，CLIC1低表达组（n = 28；<1.72倍）的5年生存率高于CLIC1高表达组（n = 28；≥1.72倍）（对数秩检验，p = 0.0300）。实验结果表明，CLIC1的过表达是胃癌潜在的预后标志物。
