Functions And Mechanism Of FAT4 As A Tumor Suppressor In Gastric Cancer

Part ⅠFunctions and mechanism of FAT4 as a tumor suppressor in gastric cancerBackground:FAT4, a cadherin-related protein, was shown to function as a tumor suppressor; however, its role in human gastric cancer remains largely unknown. Here, we investigated the role of FAT4 in gastric cancer and examined the underlying molecular mechanisms.Methods:The expression of FAT4 was evaluated by immunohistochemistry, western blotting, and qRT-PCR in relation to the clinicopatho logical characteristics of gastric cancer patients. The effects of FAT4 silencing on cell proliferation, migration and invasion were assessed by the MTT assay, migration and invasion assays in gastric cancer cell lines in vitro and in a mouse xenograft model in vivo.Results:Downregulation of FAT4 expression in gastric cancer tissues compared with adjacent normal tissues was correlated with lymph node metastasis and poor survival. Knockdown of FAT4 promoted the growth and invasion of gastric cancer cells via the activation of Wnt/β-catenin signaling, and induced EMT in gastric cancer cells, as demonstrated by the up-and down-regulation of mesenchymal and epithelial markers. FAT4 silencing promoted tumor growth and metastasis in a gastric cancer xenograft model in vivo.Conclusion:FAT4 plays a tumor suppressor role mediated by the modulation of Wnt/β-catenin signaling, providing potential novel targets for the treatment of gastric cancer.Part ⅡWeighted gene co-expression network analysis identify biomarkers of gastric cancer on expression arrayBackground:Gastric cancer(GC) is one of leading causes of cancer mortality worldwide. However the knowledge of molecular markers on gastric cancer are still limited. Gene expression profiling has provided an opportunity to understand the diversity of cancers and shown great promise in accurate prediction of prognosis and therapeutic response. A large number of gene expression data have been published since microarrays expression analysis was established more than a decade ago. Co-expression analysis was an important method to explore the relationship between genes. In this study, with the aim of identify the molecular marker of gastric cancer, we applied the methods of weighted gene co-expression network analysis (WGCNA)Methods:We collected rawdatas of five datasets(GSE13911, GSE29272, GSE35809, GSE15459, GSE38749) from GEO database and Arrayexpress database. We applied R/Bioconductor package "gcRMA". "affy". "sva". "limma", "wgcna" and "’survival" to analysis this datasets. We use DAVID database to carry out GO and KEGG pathway enrichment analysis.Results:We identified 1161 differential genes between paired gastric cancer and normal tissue. We got 11 co-expression modules. And found brown, yellow and purple modules significantly associated with the lauren types of GC. Yellow, red, turquoise, magenta and pink modules were significantly associated with the differentiation of GC. Magenta, greenyellow, black,and brown modules were significantly associated with the T stage of GC. Greenyellow, black, blue and yellow modules were significantly associated with the N stage of GC. We got eigengene of each module and calculate the correlation coefficient of each gene with module eigengene and clinical traits. At the end we got 160 probes significantly associated with the prognosis of GC.Conclusion:WGCNA is a useful method to analysis expression microarray. We got a lot of meaningful results between genes and clinical traits and some of them Deserves further study.Part IIIOpen versus Laparoscopy-Assisted D2 Radical Gastrectomy in Advanced upper Gastric CancerBackground:We conducted this study to compare open versus laparoscopy-assisted D2 radical gastrectomy in advanced upper gastric cancer.Methods:We reviewed 84 advanced gastric cancer patients who had pancreas-and-spleen preserving D2 lymph node dissection between March 2008 and March 2012. A comparative study was made about the short-term and long-term effect between laparoscopy-assisted D2 radical gastrectomy(LAG) on 41 patients and open D2 radical gastrectomy(OG) on 43 patients.Results:The clinical characteristics of patients in the two groups were well matched. Operative findings, postoperative recovery, morbidity, pathological findings in the two groups were also similar. The mean operating time was significantly longer for the LAG group (p=0.001); The Estimated blood loss reduced significantly in the LAG group (p= 0.010). The mean number of days when body temperature exceeded 37℃ and number of days to get out of bed were significantly shorter in the LAG group (p=0.001 and p=0.014 respectively). There were no postoperative deaths in both groups. The postoperative morbidity rate was 14.63% in the LAG group and 23.26% in the OG group with no significant difference (p= 0.314). The overall survival rates were 58.5% and 60.5% in the LAG and OG groups, respectively. The estimated mean survival time is 35.768 months in the LAG group and 38.664 months in the OG group, respectively. There was no statistically significant difference in the overall survival rate for patients in both groups.Conclusion:As for the advanced gastric cancer patient who is suitable for pancreas-and-spleen preserving D2 radical gastrectomy, LAG is a safe and feasible procedure with adequate lymphadenectomy, good curability and survival rate.