| Part one The expression and clinicopathologic features of YAP1,MMP14 and AJUBA in ESCC tissue in addition to prognostic significantObjective: Identification the expression of YAP1,MMP14 and AJUBA.And then discrimination the relationship between them and clinical features.Eventually,explore the survival meaning of them.Methods:1 142 cases of ESCC samples diagnosed with primary ESCC from the Department of Pathology of the Second Hospital of Hebei Medical University in the period from January 2010 to September 2015 were collected.111 cancer adjacent samples of more than 5cm distance to lesions were also acquired.The patients who involved in this research did not undergo chemotherapy or radiotherapy before surgery.Follow-up and clinicopathologic features such as gender,age,tumor differentiation,lympha metastasis and TNM stage were gathered.2 YAP1,MMP14 and AJUBA protein levels were detected by Immunohistochemistry method.The chi-square and Spearman tests were used to analyze among YAP1,MMP14,AJUBA and clinicopathologic features.3 Telephone follow-up was utilized to get overall survival time.Kaplan-Meier and COX regression analyses were used to explore the impacts of YAP1,MMP14,AJUBA and clinicopathologic features on prognosis.And survival curves were drawn.Results:1 The expressions of YAP1,MMP14 and AJUBA were higher in ESCC tumor tissues than in adjacent ones(P<0.05).2 YAP1 and MMP14 were only strongly related to lymphatic metastasis(P<0.05).MMP14 and AJUBA were only intensely correlated with TNM stage(P<0.05).3 There was no relationship between MMP14 and many other clinical feathers such as gender,age,tumor differentiation(P>0.05).Neither were YAP1 and AJUBA(P>0.05).In addition,YAP1 wasn’t associated with TNM stage(P>0.05).And AJUBA was not correlated with lymphatic metastasis(P>0.05).4 YAP1 had positive correlations separately with MMP14 and AJUBA in Spearman analysis(P<0.05).But there was not any relationship between MMP14 and AJUBA(P>0.05).5 Both of TNM stage and MMP14 had relationships with prognosis.Patients who were in Ⅲ/Ⅳ stage or had a high IHC scores of MMP14 might have a shorter survival time(P<0.05).While YAP1,AJUBA and other clinical features were not related to cancer prognosis.Part two Meta-analysis on relationship of YAP1 with common alimentary system cancersObjective: Hippo signaling pathway is a critical pathway because of its regulation organ size and carcinogenesis.Numerous researchers pay attention to it for its crosstalk with various other pathways.Plenty of studies have explored the associations of YAP1 and many types of alimentary system such as liver cancer,stomach cancer,colon cancer and esophageal cancer.However,whether YAP1 can be treated as an independent prognostic factor remains controversial.We aimed to systematically evaluate the possibility of YAP1 influencing digestive system carcinoma patients survival time,and to complement Part1 by enlarging the sample size.Method:1 We listed a comprehensive literature search strategy for study inclusion and exclusion,including types of research objects,test methods and whether have survival analysis.2 Based on search strategy,search work was made in PubMed,Cochrane Library and Web of Science databases from January 2000 to October 2016.3 Two researchers were involved in the data extract.If their search results were contradictory,another researcher was engaged to arbitration.Information about research papers such as author,year of publication,cancer type,basic information about the research queue,survival analysis was collected.4 After heterogeneity analysis,hazard ratio(HR)and 95% confidence interval(95%CI)were pooled.Which kind of effect models was chosen would be based on c2 test whose results were indicated by P value and I2 in STATA 11.0.5 Using funnel plots and Egger’s test,publication bias were evaluated.And sensitivity analysis was used to assess the robustness of the result.Result:1 Totally 16 studies from 2009 to 2015 including 2123 cases were analyzed in Meta-analysis,including China,Korea and Japan.Liver cancer,ESCC,gastric carcinoma and CRC were included.2 Heterogeneity was noticeable among these studies,so we pooled effect size with random effect model(HR=1.634,95%CI = 1.076-2.192).The results of Begg’s and Egger’s tests showed there is no publication bias,and the consequence was robust with the sensitivity analysis.Conclusions:1 YAP1,MMP14 and AJUBA were highly expressed in ESCC.They might involve themselves in tumorigenesis.2 YAP1 and MMP14 might be related to lymphatic metastasis of ESCC,and MMP14 and AJUBA were likely to be correlated with TNM stage of ESCC.YAP1,MMP14 and AJUBA probably contributed to cancer invasion and metastasis.3 Maybe YAP1 was cooperated with MMP14 and AJUBA,and they might be associated with carcinogenesis of ESCC.4 TNM stage and MMP14 were independent risk factors of overall survival in ESCC patients.5 The expression of YAP1 was closely associated with poor prognosis in digestive system cancer.YAP1 might act as a marker of shorter overall survival,suggesting it maybe a potential therapeutic target of alimentary carcinoma. |
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