Relationship Between Methylation Of SOX17Gene And Expression Of SOX17

Objective: Gastric cardia adenocarcinoma(GCA) is a kind of digestivesystem malignant tumour frequently, one type of esophagogastric junctioncancer, there was a increasing tendency in morbility and mortality.Havingbeen solated as a separated disease, GCA is receiving more and more concern.When the GCA was discovered,it has been middle-end stage and the therapyis inefficient. It is necessary to conduct a research of its pathogenesis todecrease morbidity and mortality of GCA.In recent years, more and more scientists made focus on DNA promotermethylation which has been a hot problem.The purpose of this study was toinvestigate the methylation status, the mRNA and protein expression ofSOX17gene in GCA and corresponding non-cancerous tissues. We willexplore the relationship between gene methylation and the carcinogenesis,infiltration, pathological differentiation, and metastasis of GCA, which willprovide a new theory and experiment evidence for pathogenesy, gene therapyimmunotherapy and clinical prognosis of GCA.Methods:1We examined the methylation status of the5' CpG island of SOX17genein95tumors and corresponding adjacent non-cancerous tissues,which wasused methylation specific PCR (MSP) method.2We examined the mRNA expression of SOX17gene in40cases of tumorsand corresponding adjacent non-cancerous tissues, which was used RT-PCR method.3We anlysis the protein expression of SOX17gene in78cases of tumorsand corresponding adjacent non-cancerous tissues, which was usedImmunohistochemistry (IHC) method.4We used Immunohistochemistry (IHC) method to anlysis β-catenin protein expression in78tumors and corresponding adjacent non-cancerous tissuesand the correlation of SOX17protein expression and β-catenin expression.5We analyzed the results of experiment applied SPSS13.0.Results:1SOX17gene was methylated in78of95GCA tissue(s82.1%)and60of95corresponding adjacent non-cancerous tissues(53.3%); the methylationrate of GCA tissues was higher than corresponding non-cancerous tissuessignificantly(P=0.007). Methylation frequencies of SOX17gene in welldifferentiation group85%(34/40) was higher than poor-moderate andmoderate differentiation groups80%(44/55), but did not show differencesignificantly(P>0.05). No correlation was faund between methylationstatus of SOX17gene and the other clinical data(P>0.05).2Expression level of SOX17gene mRNA in GCA was lower significantlycompared with the corresponding adjacent non-cancerous group(P=0.007).In the40GCA tissues, there was no significant correlation betweenSOX17mRNA expression quantity and gender, age,pathological type,pathological grade,lymphatic metastasis status(P>0.05).3The protein expression of SOX17gene was47.4%(37/78)in GCA,which was lower than corresponding adjacent non-cancerous(69.2%,54/78,P=0.006). Ⅲ, Ⅳ stage wassignificantly lower thanⅠⅡ(P=0.045),there was no significantly correlation between SOX17protein expressionquantity and gender, age,pathological, type, pathological grade,lymphaticmetastasis status(P>0.05).4The mRNA expression level of SOX17in methylated group in GCA was(0.365±0.144),and unmethylated group wa(s0.423±0.108),no differencewas found between methylated and unmethylated tissues(P=0.174).5The rate of SOX17protein expression in methylated group was44.30%,and the rate in unmethylated group was58.8%.There were no significantlydifference between methylated and unmethylated tissues(P=0.288).6The ectopic expression rate of β-catenin was83.3%in GCA, which wassignificantly more frequent than corresponding adjacent non-cancerous tissues(χ2=8.341, P=0.004). we also found negative correlation betweenSOX17and β-catenin protein expression(r=-0.264).Conclusions:1Hypermethylation of SOX17gene may be one of mechanism of GCA.2The ectopic expression rate of β-catenin in GCA was higher dramaticallythan correspongding adjacent non-cancerous tissues, which indicated thatWnt singnaling pathway may be aberrantly activated in GCA.3There was dramatically correlation between protein expression of SOX17gene and ectopic expression of β-catenin protein, which showed thatsilenceing of SOX17was a reason of aberrant expression of β-cateninprotein,and contributed to aberrant activation of Wnt signaling in GCA.4There was no correlation between the methylation status and protein ofSOX17and gender, age, pathological type, pathological grade, lymphaticmetastasis status, but protein expression was related to TNM, whichindicated that detection of SOX17protein expression was value forprognosis of GCA.