| Objective:This study is aimed to evaluate the diagnostic value of mesothelin in ovarian cancer and to figure out the possible mechanism of mesothelin in carcinogenesis and development.Methods:Clinical studies on the diagnosis of ovarian cancer using quantitative analysis of mesothelin were selected via searching Pubmed,Embase,Cochrane,Medline,CBM,CNKI,and Wangfang Data from the building date to October 2019.Then we screened these studies based on the inclusive and exclusive criteria and summarized the sensitivity and specificity of mesothelin for OC diagnosis.Meta-regression was performed to determine the heterogeneity and all the analyses were processed by Revman 5.3 and Stata 14.0 software.Meanwhile,the online tool GEPIA and Oncomine were used to determine the differential expression of MSLN between malignant and normal ovarian tissues.The RNA-Seq and related clinical characteristics of OC patients were downloaded from TCGA database and then used to explore the relationship ofMSLN and clinicopathologies and the prognostic value of MSLN in OC using Kaplan-Meier.We divided OC patients into MSLN-high group and MSLN-low group based on the median expression level of MSLN and then filtered the differential expressed genes.The online tool STRING was used to build protein-protein interaction(PPI)network and analyze the Gene Ontology(GO)and KEGG pathway of these genes.GCBI online laboratory was applied to predict the possible molecular mechanism.Results:A total of 20 studies were included with 1304 OC patients and 2687 control group.And the RNA-Seq and clinicopathologies data of 498 OC patients were selected from TCGA database.Results were as follows: 1.The estimated sensitivity of mesothelin for the diagnosis of OC was 0.69 and specificity was 0.94.The area under curve(AUC)of the systematic receiver operating curve(SROC)was 0.93.The diagnostic odds ratio was 37.2.The threshold effect was not the crucial reason for the high heterogeneity.Subgroup analysis showed the main reasons for heterogeneity were the study country,the way how the threshold was set,and ELISA testing kits.3.The expression level of MSLN was significantly up-regulated in different histological types of OC than normal ovarian tissue.TCGA data showed no obvious relationship between MSLN level and most clinical characteristics including patient’s age,clinical stage,histology grade,lymphovascular and vascular invasion.But MSLN expression level was significantly related to tumor status.4.The median progression-free survival(PFS)and overall survival(OS)in MSLN-high group were 18.17 months and 1484 days while the PFS and OS in MSLN-low group were 21.12 months(p=0.058)and 1583 days(p=0.137).5.Via analyzing the genomic data of MSLN-high and MSLN-low group,we screened 50 differential expressed genes.GO enrichment analysis showed the main biological process were mitotic cell cycle process,microtubule cytoskeleton organization involved in mitosis and cell division.And the KEGG pathway was p53 signaling pathway.6.PPIanalysis showed an interaction during MSLN,MUC16,FOLR1,and UPK3 B.And MSLN,MUC16.And MSLN,MUC16,and FOLR1 formed a relatively closed triangular signal cycle.MSLN expression level was positive related with MUC16,FOLR1,and UPK3 B.GCBI indicated many common transcription factors in MSLN/MUC16,MSLN/FOLR1,and MSLN/UPK3 B.Conclusions:Mesothelin emerges as a promising diagnostic biomarker in ovarian cancer.And its high expression pattern makes it a prognostic marker for patients with ovarian cancer,which requires for more large scale studies to verify.Besides,the interaction between MSLN/MUC16,MSLN/FOLR1,and MSLN/UPK3 B indicate their applicability in targeted treatments. |
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