Background: Activation of MEK5 in many cancers is associated with carcinogenesis through aberrant cell\r\nproliferation. In this study, we determined the level of phosphorylated MEK5 (pMEK5) expression in human\r\ncolorectal cancer (CRC) tissues and correlated it with clinicopathologic data.\r\nMethods: pMEK5 expression was examined by immunohistochemistry in a tissue microarray (TMA) containing 335\r\nclinicopathologic characterized CRC cases and 80 cases of nontumor colorectal tissues. pMEK5 expression of 19\r\ncases of primary CRC lesions and paired with normal mucosa was examined by Western blotting. The relationship\r\nbetween pMEK5 expression in CRC and clinicopathologic parameters, and the association of pMEK5 expression\r\nwith CRC survival were analyzed respectively.\r\nResults: pMEK5 expression was significantly higher in CRC tissues (185 out of 335, 55.2%) than in normal tissues\r\n(6 out of 80, 7.5%; P < 0.001). Western blotting demonstrated that pMEK5 expression was upregulated in 12 of 19\r\nCRC tissues (62.1%) compared to the corresponding adjacent nontumor colorectal tissues. Overexpression of\r\npMEK5 in CRC tissues was significantly correlated to the depth of invasion (P = 0.001), lymph node metastasis (P <\r\n0.001), distant metastasis (P < 0.001) and high preoperative CEA level (P < 0.001). Consistently, the pMEK5 level in\r\nCRC tissues was increased following stage progression of the disease (P < 0.001). Analysis of the survival curves\r\nshowed a significantly worse 5-year disease-free (P = 0.002) and 5-year overall survival rate (P < 0.001) for patients\r\nwhose tumors overexpressed pMEK5. However, in multivariate analysis, pMEK5 was not an independent prognostic\r\nfactor for CRC (DFS: P = 0.139; OS: P = 0.071).\r\nConclusions: pMEK5 expression is correlated with the staging of CRC and its expression might be helpful to the\r\nTNM staging system of CRC.
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