Expression and clinical significance of the DNA repair enzyme MYH in esophageal squamous cell carcinoma.

MYH is an important enzyme in combating DNA oxidative stress in the occurrence and development of various types of tumors. To investigate the correlation between expression of the DNA repair enzyme MYH in esophageal squamous cell carcinoma and 8-oxoguanine (8-oxoG) oxidative damage, as well as the clinical significance of altered MYH expression, tissues from 175 esophageal carcinoma cases were investigated in the present study. MYH expression and 8-oxoG oxidative damage in squamous cell carcinoma and adjacent normal tissue were assessed by immunohistochemistry and Western blotting. In 82.9% (145/175) of the cases, MYH protein expression in esophageal squamous cell carcinoma was lower than that of adjacent normal tissue (t=4.24, P<0.001). Additionally, 8-oxoG staining was higher in the tumors than in the normal tissue. Lower expression of MYH in esophageal squamous cell carcinoma was associated with depth of invasion, venous invasion, TNM stage and lymph node metastasis (P<0.05). In conclusion, a lower MYH expression level in esophageal cell carcinoma tissue was inversely associated with more severe 8-oxoG oxidative damage, suggesting that changes in MYH activity correspond to increased DNA damage in tumor cells. The use of MYH expression as a postoperative index for esophageal squamous cell carcinoma may guide the formulation of individualized chemotherapy for patients after surgery.

[1]  Nan Hu,et al.  Global Gene Expression Profiling and Validation in Esophageal Squamous Cell Carcinoma and Its Association with Clinical Phenotypes , 2011, Clinical Cancer Research.

[2]  Magnar Bjørås,et al.  Separation-of-function mutants unravel the dual-reaction mode of human 8-oxoguanine DNA glycosylase. , 2011, Structure.

[3]  A. Blomberg,et al.  Evolutionary loss of 8-oxo-G repair components among eukaryotes , 2010, Genome Integrity.

[4]  C. N. Leitão,et al.  Aggressive Phenotype of MYH-Associated Polyposis with Jejunal Cancer and Intra-Abdominal Desmoid Tumor: Report of a Case , 2009, Diseases of the colon and rectum.

[5]  W. Guo,et al.  An investigation on the polymorphisms of two DNA repair genes and susceptibility to ESCC and GCA of high-incidence region in northern China , 2009, Molecular Biology Reports.

[6]  J. Gisbert,et al.  Identification of MYH mutation carriers in colorectal cancer: a multicenter, case-control, population-based study. , 2007, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[7]  E. Montgomery,et al.  Duodenal reflux leads to down regulation of DNA mismatch repair pathway in an animal model of esophageal cancer. , 2007, The Annals of thoracic surgery.

[8]  K. Hersey,et al.  MYH mutations are rare in prostate cancer , 2007, Journal of Cancer Research and Clinical Oncology.

[9]  A. Lu,et al.  MutY and MutY homologs (MYH) in genome maintenance. , 2006, Frontiers in bioscience : a journal and virtual library.

[10]  L. Roberts,et al.  MYH Y165C and G382D mutations in hepatocellular carcinoma and cholangiocarcinoma patients , 2006, Journal of Cancer Research and Clinical Oncology.

[11]  K. Miyazaki,et al.  Allelic loss of the DNA repair gene OGG1 against oxidative damage in esophageal squamous cell carcinoma. , 2005, Oncology reports.

[12]  J. Miller,et al.  Enhanced activity of adenine-DNA glycosylase (Myh) by apurinic/apyrimidinic endonuclease (Ape1) in mammalian base excision repair of an A/GO mismatch. , 2001, Nucleic acids research.

[13]  E. Dekker,et al.  Hyperplastic polyps and sessile serrated adenomas as a phenotypic expression of MYH-associated polyposis. , 2008, Gastroenterology.

[14]  E. Montgomery,et al.  Selective decrease in the DNA base excision repair pathway in squamous cell cancer of the esophagus. , 2007, The Journal of thoracic and cardiovascular surgery.

[15]  D. Barnes,et al.  Advances in Brief Accumulation of the Oxidative Base Lesion 8-Hydroxyguanine in DNA of Tumor-Prone Mice Defective in Both the Myh and Ogg 1 DNA Glycosylases , 2004 .