The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, China.
BMC Cancer. 2012 Mar 30;12:127. doi: 10.1186/1471-2407-12-127.
Activation of MEK5 in many cancers is associated with carcinogenesis through aberrant cell proliferation. In this study, we determined the level of phosphorylated MEK5 (pMEK5) expression in human colorectal cancer (CRC) tissues and correlated it with clinicopathologic data.
pMEK5 expression was examined by immunohistochemistry in a tissue microarray (TMA) containing 335 clinicopathologic characterized CRC cases and 80 cases of nontumor colorectal tissues. pMEK5 expression of 19 cases of primary CRC lesions and paired with normal mucosa was examined by Western blotting. The relationship between pMEK5 expression in CRC and clinicopathologic parameters, and the association of pMEK5 expression with CRC survival were analyzed respectively.
pMEK5 expression was significantly higher in CRC tissues (185 out of 335, 55.2%) than in normal tissues (6 out of 80, 7.5%; P < 0.001). Western blotting demonstrated that pMEK5 expression was upregulated in 12 of 19 CRC tissues (62.1%) compared to the corresponding adjacent nontumor colorectal tissues. Overexpression of pMEK5 in CRC tissues was significantly correlated to the depth of invasion (P = 0.001), lymph node metastasis (P < 0.001), distant metastasis (P < 0.001) and high preoperative CEA level (P < 0.001). Consistently, the pMEK5 level in CRC tissues was increased following stage progression of the disease (P < 0.001). Analysis of the survival curves showed a significantly worse 5-year disease-free (P = 0.002) and 5-year overall survival rate (P < 0.001) for patients whose tumors overexpressed pMEK5. However, in multivariate analysis, pMEK5 was not an independent prognostic factor for CRC (DFS: P = 0.139; OS: P = 0.071).
pMEK5 expression is correlated with the staging of CRC and its expression might be helpful to the TNM staging system of CRC.
MEK5 在许多癌症中的激活与通过异常细胞增殖导致的癌变有关。在这项研究中，我们测定了人结直肠癌（CRC）组织中磷酸化 MEK5（pMEK5）的表达水平，并将其与临床病理数据相关联。
通过免疫组织化学法在包含 335 例临床病理特征明确的 CRC 病例和 80 例非肿瘤结直肠组织的组织微阵列（TMA）中检测 pMEK5 的表达。通过 Western blot 法检测 19 例原发性 CRC 病变及其配对正常黏膜中的 pMEK5 表达。分别分析 CRC 中 pMEK5 的表达与临床病理参数的关系，以及 pMEK5 表达与 CRC 生存的相关性。
CRC 组织中 pMEK5 的表达明显高于正常组织（335 例中的 185 例，55.2%比 80 例中的 6 例，7.5%；P<0.001）。Western blot 法显示，与相应的相邻非肿瘤结直肠组织相比，19 例 CRC 组织中有 12 例（62.1%）pMEK5 表达上调。CRC 组织中 pMEK5 的过度表达与浸润深度（P=0.001）、淋巴结转移（P<0.001）、远处转移（P<0.001）和术前 CEA 水平升高（P<0.001）显著相关。一致地，CRC 组织中 pMEK5 的水平随着疾病分期的进展而增加（P<0.001）。生存曲线分析显示，pMEK5 过度表达的患者的 5 年无病生存率（P=0.002）和 5 年总生存率（P<0.001）显著更差。然而，在多变量分析中，pMEK5 不是 CRC 的独立预后因素（DFS：P=0.139；OS：P=0.071）。
pMEK5 的表达与 CRC 的分期相关，其表达可能有助于 CRC 的 TNM 分期系统。
