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The Expression Of VEGF,β-catenin,DKK1 In Malignant Melanoma And The Relationship With Prognosis

Posted on:2018-06-16Degree:MasterType:Thesis
Country:ChinaCandidate:Y F DaiFull Text:PDF
GTID:2334330533470959Subject:Oncology
Abstract/Summary:PDF Full Text Request
Objectives 1 retrospective analysis: To analyze and explore the situation of admission and treatment of malignant melanoma(MM)by Tumor Hospital Affiliated to Tianjin Medical University from 2005-01-01 to 2009-12-31 and to find which factor could affect MM’s prognosis.2 analysis of gene expression: First of all,we would investigate the expression of VEGF,β-catenin and DKK1 gene in 30 cases of CMM(cutaneous malignant melanoma)group and the control group of normal skin around the tumor admitted and treated from 2005-01-01 to 2009-12-31 by Tumor Hospital Affiliated to Tianjin Medical University,and analyze the relationships among the above genes and the relationship between the above genes and the lymphatic metastasis or prognosis of CMM.Then we could probe or explore the mechanism of molecular biology about CMM,prognostic factors of CMM,and provide some ideas of researching and developing of targeted drugs in sake of curing the disease.Methods 1 retrospective analysis: We would collect some MM cases that diagnosed by histopathology and admitted and treated from 2005-01-01 to 2009-12-31 by Tumor Hospital Affiliated to Tianjin Medical University.In addition to that,these cases should have complete data information.Methods of follow-up were medical records querying,telephoning,and the deadline was 2016-05-31.The survival time was the day that from confirmed by pathophysiology to follow-up day,and the unit was month,except for the value of survival cases were defined as censoring data.The disease staging standard was the 7 edition of AJCC(American Joint Committee on Cancer)2010 of melanoma’s TNM staging criteria.After screening(excluding few cases of freckle types and few cases of dying from other diseases),190 cases of MM patients were enrolled and the data were analyzed and constructed.SPSS 17.0 simplified Chinese version was used as the software of analyzing statistically.First,we select 13 factors such as tumor thickness,age,sex,pathological stage,pathologic type,onset of lymph node metastasis,ulcer,satellite lesion,metastatic lymph node count,surgical resection,intervention history,comprehensive treatment and radiotherapy history that may affect prognosis of MM,then we adopted the life table method to analyze the survival time and survival rate,Log-rank test of Kaplan-Meier to be as the method of univariate survival analysis,COX regression model to be as the method of multivariate survival analysis for those who statistically significant in univariate analysis.When the value of P<0.05,we thought it was statistically significant.2 gene expression analysis: First,we random collected 30 CMM cases that diagnosed by histopathology and admitted and treated from 2005-01-01 to 2009-12-31 by Tumor Hospital Affiliated to Tianjin Medical University,and these cases should have complete data information.We adopted these cases into CMM group,and the corresponding normal tissue around the tumor were included in the control group.Methods of follow-up were medical records querying,telephoning,and the deadline was 2016-05-31.The survival time was the day from confirmed by pathophysiology to following up day,and the unit was month,except for the value of survival cases were defined as censoring data.Then the method of HE staining was adopted for the reconfirmation of the organization’s sources,two-step of SP staining of immunohistochemistry was adopted for the expression of VEGF,β-catenin,DKK1.Those who qualified cases of dying(26 cases of VEGF,22 cases of β-catenin and 25 cases of DKK1)expression and corresponding information would be register into the database,after that,software of SPSS 17.0 Simplified Chinese version was adopted for statics analysis.ChiSquare Test was used to analyze the differences in gene expressions between CMM group and control group.The correlation analysis of spearman was used to analyze the expressionof each gene mutually and the expression between each gene and the lymphatic metastasis in the CMM group.The log-rank test of Kaplan-Meier method of univariate survival analysis was used to detect the relationship of expression of each gene with prognosis of CMM group.When the value of P<0.05,we thought it was statistically significant.Results 1 retrospective analysis: 1)The total number of MM patients admitted and treated by Tumor Hospital Affiliated to Tianjin Medical University was 48 cases,28 cases,43 cases,62 cases and 64 cases respectively in 5 years.As of the follow-up day of 2016-05-31,there were 134 patients died.The overall survival rates were 77.9%,52.6%,38.4% respectively,and the total MST(median survival time)was 43 months.2)Univariate survival analysis showed that the factors of lymph node metastasis,pathological type,surgical resection,tumor thickness,comprehensive treatment,numbers of lymph node metastasis,ulcer and pathological stage,could affect the prognosis of MM patients(P<0.05).3)The pathological stage,comprehensive treatment,surgical resection range and tumor thickness were the independent prognostic factors of long-term survival of patients with MM(P<0.05),and the value of RR of tumor thickness was 1.307,RR of pathological staging was 1.450,RR of comprehensive treatment was 0.812,RR of surgical resection range was 0.775.2 analysis of gene expression: 1)The positive rate of VEGF,β-catenin and DKK1 in CMM group and control group were 17(65.4%)vs 7(26.9%),15(68.2%)vs 4(18.2%),and 17(68.0%)vs 5(20.0%).The differences expression of the three genes in different groups were statistically significant(P<0.05,c2vegf=4.776,c2β-catenin=9.823,c2DKK1=11.688).2)Univariate survival analysis showed that the differential expression of VEGF and β-catenin in CMM was statistically significant(P<0.05,c2vegf=16.359,c2β-catenin=7.475).The difference of DKK1 expression was not statistically significant(P>0.05).3)The expression of VEGF,β-catenin and DKK1 were positively correlated with lymphatic metastasis(P<0.05,the value of r VEGFlymphatic metastasis was 0.409,rβ-catenin-lymphatic metastasis was 0.428,r DKK1-lymphatic metastasis was 0.514).4)There was a positive correlation between the gene of VEGF or β-catenin’s expression(P<0.05,r VEGF-β-catenin=0.447).There was no statistical correlation between the expression of VEGF and β-catenin and the expression of DKK1(P>0.05).Conclusions 1 retrospective analysis: 1)The overall rate of MM admission and treatment in the past 5 years by Tumor Hospital Affiliated to Tianjin Medical University has an increasing trend,and the long-term prognosis of MM patients was poor.2)The factors such as lymph node metastasis,pathological type,surgical resection,tumor thickness,comprehensive treatment,numbers of lymph node metastasis,ulcer and pathological stage could affect the prognosis of MM patients(P<0.05).3)The pathological stage and tumor thickness(risk factors),surgical resection range andc omprehensive treatment(protective factors)were the independent prognostic factors of long-term survival of patients with MM(P<0.05).2 analysis of gene expression: 1)The positive expression of VEGF,β-catenin and DKK1 in CMM group were increased,the three genes may play a role in the development of CMM.2)The VEGF and β-catenin gene could influence the prognosis of CMM,both of which could be used as predictors of CMM’s survival expectancy.3)The gene of VEGF,β-catenin and DKK1 may be involved in CMM lymph node metastasis.4)The VEGF and β-catenin gene may developed synergism or some association in the development of CMM.
Keywords/Search Tags:melanoma, prognosis, VEGF, β-catenin, DKK1
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