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Expression Of D0K3 In Early Gastric Cancer And Precancerous Lesion And Its Effect On The Proliferation And Invasion Of HGC-27 Gastric Cancer Cells And The Pathological Differences Of Endometrial Biopsy And Resection

Posted on:2017-02-14Degree:DoctorType:Dissertation
Country:ChinaCandidate:J F CuiFull Text:PDF
GTID:1104330488467900Subject:Digestive medicine
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AimTo explore the expression of DOK3 inearly gastric cancer and precancerous lesions and its effect on proliferation, migration and invasion of HGC-27 gastric cancer cell line.MethodsThe expression levels of DOK3 protein in 35 cases of chronic superficial gastritis,13 cases of LGIN,38 cases of HGIN and 24 cases of EGC were detected by immunohistochemistry. DOK3 mRNA and protein levels of expression were detected by real time PCR and Western Blot in three gastric cancer cell lines.Then human gastric cancer cell were transfected with siRNA specific for DOK3, the effects of gene silencing were analyzed at the transcriptional and translational levels. The effects of gene silencing on cell proliferation,cell invasion and migration migration were analyzed using CCK-8 and wound healing assay, respectively.Results(1) The positive expression rates of DOK3 in chronic superficial gastritis group, low grade intraepithelial neoplasia group, high grade intraepithelial neoplasia group and early gastric cancer group were 80%,61.5%,52.5%,37.5%, respectively. Rate of positive expression of DOK3 in chronic superficial gastritis tissue was significantly higher than that of high grade intraepithelial neoplasia group and early gastric cancer group (P< 0.05), there was no statistical significance between chronic superficial gastritis group and low grade intraepithelial neoplasia group,low grade intraepithelial neoplasia group and high grade epithelial in neoplasia group (P>0.05).(2) Real time PCR and western blot analyses showed that DOK3 in gastric cancer cell were low expression, the expression levels of DOK3 from high to low were HGC-27, MGC-803, and AGS, respectively.(3)Real time PCR and western blot analyses showed that when the DOK3 gene was silenced, DOK3 protein expression was significantly downregulated, the cell proliferation,cell invasion and migration were significantly enhanced(P<0.05).Conclusion(1) The positive expression rate of DOK3 in EGC and HGIN were significantly lower than that of chronic superficial gastritis and LGIN, suggesting that DOK3 may be an early important biological events in gastric carcinogenesis which may be related to the occurrence and development of gastric cancer,it may have a certain molecular biological diagnostic value.(2) When the DOK3 gene was knocked down, the HGC-27cell line proliferation,cell invasion and migration were significantly enhanced, suggesting that DOK3 may be a tumor suppressor gene.AimGastric intraepithelial neoplasia (GIEN) is precancerous lesion of gastric cancer.Diagnosis of gastric intraepithelial neoplasia with endoscopic forceps biopsy (EFB) is controversial in the era of endoscopic resection (ER). Our aim was to investigate the diagnostic reliability of EFB in patients with GIEN compared with ER specimens.MethodsFrom January 2010 to march 2015 98 cases were diagnosed GIEN by EFB in Peking Union Medical College Hospital, including 20 case of low-grade gastric intraepithelial neoplasia (LGIN),65 case of high-grade gastric intraepithelial neoplasia (HGIN), and 13 case of gastric carcinomas. All patients were treated with ER. The discrepancy of preoperative and postoperativepathological rate, clinic characteristics, and endoscopic factors were analyzed.ResultsThe overall histological discrepancy rate between EFB and ER specimens was 55.1% among the enrolled patients. For 20 cases with LGIN on EFB,12 cases were finally diagnosed as a higher grade neoplasia such as HGIN (35%,7/20) or carcinoma (25%,5/20) by the results of ER. For 65 cases with HGIN on EFB,38 cases were finally diagnosed as carcinoma after ER (major histological discrepancy rate:58.5%,38/65).the size>2cm in diameter, the surface colour-erythema were associated with the histological discrepancy between EFB and ER specimens(P< 0.001,P<0.05 respectively).ConclusionsThe reliability of endoscopic forceps biopsy in the definitive diagnosis of gastric intraepithelial neoplasia is not well. ER should be considered as not only definitive treatment but also a precise histological diagnosis for lesions initially diagnosed as GIEN by endoscopic forceps biopsy specimens.
Keywords/Search Tags:Early gastric cancer, Gastric high/low grade intraepithelial neoplasia, DOK3, Immunohistochemistry staining, Proliferation, Migration, Invasion, Gastric intraepithelial neoplasia, Endoscopic forceps biopsy, Endoscopic resection
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