title: Expression of the phosphorylated MEK5 protein is associated with TNM staging of colorectal cancer.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  pMEK5 expression is correlated with the staging of CRC and its expression might be helpful to the TNM staging system of CRC.
authors.affiliation: The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, China.
authors.forename: Bang
authors.initials: B
authors.lastname: Hu
authors.forename: Donglin
authors.initials: D
authors.lastname: Ren
authors.forename: Dan
authors.initials: D
authors.lastname: Su
authors.forename: Hongcheng
authors.initials: H
authors.lastname: Lin
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Xian
authors.forename: Xingyang
authors.initials: X
authors.lastname: Wan
authors.forename: Junxiao
authors.initials: J
authors.lastname: Zhang
authors.forename: Xinhui
authors.initials: X
authors.lastname: Fu
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.forename: Dechan
authors.initials: D
authors.lastname: Diao
authors.forename: Xinjuan
authors.initials: X
authors.lastname: Fan
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Jianping
authors.initials: J
authors.lastname: Wang
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D048671:MAP Kinase Kinase 5 / Q000378:metabolism*; D046228:Microarray Analysis; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D048671:MAP Kinase Kinase 5; C482563:MAP2K5 protein, human