MEK5 overexpression is associated with the occurrence and development of colorectal cancer
In this study, immunohistochemstry analysis was conducted on two groups of paraffin-embedded samples. The first group included 24 normal colorectal mucosa, 24 adenomas and 84 primary colorectal adenocarcinomas, which were randomly collected from archival tissues surgically removed at the Sixth Affiliated Hospital of Sun Yat-sen University, between 2007 and 2010. All of these samples were pathologically confirmed. The second group included 342 archival tissues specimens of CRC, which were histologically and clinically diagnosed, from the First Affiliated Hospital of Sun Yat-sen University, between January 2000 and November 2006. The cases selected were based on the following criteria: a distinctive pathological diagnosis of CRC, having undergone primary and curative resection for CRC, availability of resection tissue, availability of follow-up data, and having not received preoperative anticancer treatment. These CRC cases included 185 (54.1 %) men and 157 (45.9 %) women, with a mean age of 59.6 years. The average follow-up time was 71.5 months, and a total of 102 (30.4 %) patients died during the follow-up period. Patients whose cause of death remained unknown were excluded from our study. Tumor grades were defined in accordance with the criteria of the World Health Organization (WHO) (2000). The pathological TNM status of all CRC was defined according to the criteria of the sixth edition of the TNM classification of the International Union Against Cancer (2002). In addition, eight pairs of fresh CRC tissue specimens and normal adjacent colorectal mucosa specimens were obtained from patients with CRC who underwent surgical tissue resection at the Sixth Affiliated Hospital of Sun Yat-sen University during 2010. All of the CRC samples selected were the samples that contained at least 70 % carcinoma tissues in the whole tissue samples with the help of frozen section examination. Our study was approved by Clinical Ethics Review Committee at the Sixth Affiliated Hospital of Sun Yat-sen University (Guangzhou, China), and written informed consent was obtained from all the patients.Immunostaining of MEK5 in CRC tissues and normal mucosa was detected as brown-yellow granules in the cytoplasm (Fig. 1). In the first group object of this study, the MEK5 was overexpressed in 38.1 % of CRC tissues (32 out of 84); compared with 20.8 % of colorectal adenoma (5 out of 24) and 8.3 % of normal tissues (2 out of 24) (Fig. 1). Statistical analysis indicated that MEK5 was gradually up-regulated from normal mucosa to adenomas, and to tumor tissues (P = 0.011; Table 1). Furthermore, in some sections of colorectal adenomas and at the junctions of tumor and normal mucosa, we found that the MEK5 expression level was notably correlated with progression of CRC. MEK5 expression was normal in normal colorectal mucosa and higher in the adjacent atypical hyperplasia of the mucosa (Fig. 1-g, h).To confirm the expression levels of MEK5 seen by immunostaining in the specimens from our TMA, we examined the expression of MEK5 protein by western blot analysis in 8 randomly selected pairs of CRC tissues and their matched not-tumor colorectal tissues. In 5 of 8 (62.5 %) CRC patients, the total MEK5 protein was up-regulated in tumor tissues compared with their adjacent nontumor colorectal mucosa; furthermore, the ratio of MEK5α to MEKβ was higher in all of the CRC tissues than in their adjacent normal colorectal mucosa (Fig. 2).This study was supported by the Guangdong province natural science foundation of China S2013040016396 (Dr. Dechang Diao). We thank Liyan Cui, Megan McLaughlin, Weiling He and Daxiong Wang for their great help in writing and editing the manuscript.Competing interestsThe authors declare that they have no competing interests.Authors’ contributionsLW and DCD designed the study; DCD performed all the experiments and wrote the paper, JW, ZQC, HLL and JSP performed part of the experiments and composition of the manuscript. LNZ and WW reviewing and scoring the degree of immunostaining of sections, XLC was responsible for data collection and analysis. All authors have read and approved the final manuscript.