Wei Jin-Lai, Fu Zhong-Xue, Fang Min, Zhou Qiu-Yuan, Zhao Qing-Ning, Guo Jin-Bao, Lu Wei-Dong, Wang Hao
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, 1 You Yi Road, Chongqing, 400016, China.
Tumour Biol. 2014 Sep;35(9):9185-94. doi: 10.1007/s13277-014-2179-3. Epub 2014 Jun 14.
Calcium/calmodulin-dependent serine protein kinase (CASK), which localizes at cell-cell adhesion sites and binds to the heparan sulfate proteoglycan syndecan-2, is involved in cell proliferation, cytoskeletal remodeling, and cell migration. To demonstrate the role of CASK in colorectal cancer (CRC) carcinogenesis, we examined the expression of CASK and its binding protein syndecan-2 in human CRC tissues. The expression of CASK was measured in CRC specimens and the controls from adenomas and normal mucosae by immunohistochemical staining and Western blot analysis. Syndecan-2 protein level was tested in CRC samples and the controls by Western blot analysis. The correlations between CASK expression and clinicopathological variables, including disease-free survival (DFS) and overall survival (OS), were analyzed. Compared to the controls, both CASK and syndecan-2 expression were enhanced in CRC tissues. Furthermore, high expression of CASK and syndecan-2 was significantly correlated with advanced tumor stage, lymphatic invasion, lymph node metastasis, vascular invasion, liver metastasis, and unresectable metastatic CRC. Survival analysis showed that patients with low CASK staining had a significantly better survival compared to patients with high CASK staining. In multivariate analysis, CASK overexpression, advanced tumor stage, lymph node metastasis, vasvular invasion, and liver metastasis were independent prognostic factors of poor DFS and OS. Our present study indicates that CASK overexpression is associated with an unfavorable prognosis. CASK is an independent prognostic factor for CRC, which suggests that it is a novel and crucial predictor for CRC metastasis.
钙/钙调蛋白依赖性丝氨酸蛋白激酶（CASK）定位于细胞间黏附位点，并与硫酸乙酰肝素蛋白聚糖Syndecan-2结合，参与细胞增殖、细胞骨架重塑和细胞迁移。为了证明CASK在结直肠癌（CRC）致癌过程中的作用，我们检测了人CRC组织中CASK及其结合蛋白Syndecan-2的表达。通过免疫组织化学染色和蛋白质印迹分析检测CRC标本以及腺瘤和正常黏膜对照中CASK的表达。通过蛋白质印迹分析检测CRC样本和对照中Syndecan-2蛋白水平。分析CASK表达与临床病理变量之间的相关性，包括无病生存期（DFS）和总生存期（OS）。与对照相比，CRC组织中CASK和Syndecan-2的表达均增强。此外，CASK和Syndecan-2的高表达与肿瘤晚期、淋巴浸润、淋巴结转移、血管浸润、肝转移和不可切除的转移性CRC显著相关。生存分析表明，与CASK染色高的患者相比，CASK染色低的患者生存期明显更好。在多变量分析中，CASK过表达、肿瘤晚期、淋巴结转移、血管浸润和肝转移是DFS和OS不良的独立预后因素。我们目前的研究表明，CASK过表达与不良预后相关。CASK是CRC的独立预后因素，这表明它是CRC转移的一种新的关键预测指标。
