Methylation Status And Its Significance Of MGMT And MAL Gene In Colorectal Cancer

BackgroundColorectal cancer(CRC),whose morbidity ranks for the third of global tumorsand mortality accounts for9%of global malignancies, is one of the most commonmalignancies in gastrointestinal tract. It is always not confirmed until it has developedinto middle-late stage and often results in poor treatment effect and prognosis.Therefore, it is a key point to explore the molecular mechanisms of pathogenesis anddevelopment of CRC and find methods for early diagnosis and treatment. Until now,the recognized mechanism of silence of tumor suppressor genes and activation ofoncogenes can not explain the tumorigenesis of CRC adequately. In recent yearspeople have realized that epigenetic regulation involved in tumorigenesis. DNAmethylation is one of the earliest epigenetic regulation and has a close relation ontumorigenesis. Aberrant hypermethylation of several genes have been foundfrequently occur in CRC. O6-methylguanine-DNA–methyltransferase (MGMT),located in10q26, is expressed in all normal cells and its main function is to protectDNA against alkylating agent. The Myelin and lymphocyte-associated protein gene(MAL),located in2q13, is widely expressed in various cells and plays an importantrole in maintaining normal physiological function of cells. Studies show that MGMTand MAL gene were downregulated or silenced in many malignancies such asesophageal cancer, gastric cancer and head and neck squamous cell carcinoma and that were correlated with tumor pathogenesis and progression. However, themethylation status and its significance of MAL gene in colorectal cancer，and ifMGMT and MAL gene have synergistic effect when detected its methylation statustogether? There is few reports domestic and overseas. Furthermore, the relationshipbetween MGMT and MAL gene methylation and progression and prognosis of CRCis controversial.AimTo study the methylation status of MGMT and MAL in colorectal cancer tissuesand nomal colorectal tissues, explore the relationships between the two genes and theoccurrence and development of colorectal cancer.Methods46cases of primary CRC tissues and normal colorectal tissues(distant fromcancer core more than5cm) were prepared from the First Affiliated Hospital ofZhengzhou University between2011～2013. All specimens were diagnosed bypathology results after surgery and were not preoperative radiation and chemotherapyand immunotherapy. Methylation specific PCR (MSP) was used to detect themethylation status of MGMT and MAL genes in those tissues. Chi-square test andcorrelation analysis were used to work for statistical analysis.Results1. The methylation rates of MGMT in CRC tissues and normal colorectal tissueswere36.96%and6.52%respectively. Statistics analysis showed that difference inCRC and normal colorectal tissues was statistically significant (P<0.05). Themethylation rates of MAL in CRC tissues and normal colorectal tissues were65.22%and8.69%respectively. Statistics analysis showed that difference in CRCand adjacent tissues was statistically significant (P <0.05).2. MGMT methylation was correlated with CRC lymph node metastasis (P <0.05) but had no correlation with age, sex, tumor size or tumor satge. MAL methylationhad no correlation with those clinical features (P>0.05).3. MGMT gene methylation was related to MAL gene methylation in CRC（rp=0.370，P <0.05）.Conclusions1. MGMT and MAL gene methylation associated with the pathogenesis anddevelopment of CRC.2. MGMT methylation can cooperate with MAL methylation in CRC.3. The combined detection of MGMT and MAL gene methylation in early diagnosisof CRC may have some clinical significance.