Study Of SPG20 Gene Methylation In Primary Lung Adenocarcinoma

Lung cancer is the leading cause of cancer-related deaths in men and women. Almost 80% of bronchogenic carcinomas are non–small-cell lung cancer(NSCLC). More than half of the patients with newly diagnosed NSCLC present with metastatic disease which confers a grim prognosis, and the 5-year survival rates are less than 20%. Although cytotoxic chemotherapy offers symptom palliation and prolongation of survival, more effective treatment strategies are needed. Aberrant DNA methylation has been shown to be more frequent than genetic changes in cancer development and often represents early events.Genes that are frequently methylated in tumor samples compared to normal tissue may represent potential biomarkers for noninvasive and early detection of several cancer types, including colorectal(CRC), prostate cancer, and NSCLC. Genes with altered DNA methylation(P16, APC, RASSF1 A, CDH1, DAPK, CDH13, RARβ-2, MGMT) can be used as biomarkers for cancer detection and assessment of prognosis. Spastic paraplegia-20(SPG20) encodes Spartin, a multifunctional protein, which has previously been found to be involved in intracellular epidermal growth factor recept(EGFR) or trafficking. Prior studies have demonstrated that the promoter of the SPG20 gene was hypermethylated in colon cancer cell lines. However, to date, SPG20 hypermethylation has not been studied in AC. Here we investigated the relationship between SPG20 hypermethylation, EGFR expression and AC clinical characteristic.Objectives:1 Investigated the relationship between SPG20 hypermethylation and Spartin expression with AC clinical characteristic.2 Research the relationship between Spartin and EGFR expressions in AC.Method:A total of 58 patients with AC who were undergoing curative resection at Fourth Hospital of Hebei Medical University thoracic surgery department between January 2014 to October 2014 were enrolled in this study. The far tumor tissues corresponding to fresh cancer tissue samples(5cm above the edge of cancer tissues) as a control group. SPG20 hypermethylation were detected in both cancer and for tumor tissues. Immunohistochemistry was used to check the expression of Sparin and EGFR. The relationship between SPG20, EGFR and clinical characteristics in AC samples by SPSS19.0.Result:1 SPG20 hypermethylation and ACSPG20 hypermethylation status were detected in both AC tumor group and far tumor group of AC samples. The positive rate of SPG20 hypermethylation in AC tumor group is 60.3%(35/58). The positive rate of SPG20 hypermethylation in AC far tumor group is 12.1%( 7/58). The difference between tumor and far tumor groups are significant(P<0.01). Statistical analysis show that the positive rate of SPG20 hypermethylation in tumor group has significant relationship with TNM stag and lymph node metastasis(P<0.05). But no relationship with gender, age, and smoking(P>0.05).2 Spartin expression and ACSpartin expressions were detected by immunohistochemistry in both AC tumor group and far tumor group of AC samples. The positive rate of Spartin expression in AC tumor group is 44.8%(26/58).The positive rate of Spartin expression in AC far tumor group is 67.2%(39/58). The difference between tumor and far tumor groups are significant(P<0.05).But no relationship with TNM stag,lymph node metastasisgender, age, and smoking(P>0.05). In SPG20 methylation positive expression group, Spartin expression rate is 34.3%(12/35).In SPG20 methylation negative expression group, Spartin expression rate is 60.9%(14/23). There was significant difference between both groups of Spartin expession rate. Statisti analysis show that SPG20 hypermethylation was closely related with Spartin low expression.3 EGFR expression and ACEGFR expressions were detected by immunohistochemistry in both AC tumor group and far tumor group of AC samples. In tumor group, EGFR expression rate is 58.6%(34/58). In far tumor group, EGFR expression rate is 3.4%(2/58). There was significant difference between both groups of EGFR expession. Statistic analysis show that EGFR expression was closely related with lymph node metastasis(P<0.05).4 The relationships between SPG20 hypermethylation, Spartin expression and EGFR expression. EGFR expression rate is 23.1%(6/26)in AC tumor group with Spartin expression, but EGFR expression rate is 87.5%(28/32)in AC tumor group with Spartin negative expression. Statistic analysis show that EGFR expression was closely related with Spartin expression(P<0.01). Meanwhile, Statistic analysis show that EGFR expression was closely related with SPG20 hypermethylation(P<0.05).Conclusion:1 SPG20 hypermethylation is closely related with AC tumor.2 EGFR positive expression is closely related with AC tumor. EGFR positive expression was closely related with Spartin negative expression. SPG20 hypermethylation maybe one of the reason for EGFR expression in AC.