1.Prospective Proteomic-based Study For Identification Of Potential Biomarkers In The Diagnosis Of Solid Pseudopapillary Tumor Of Pancreas 2.The Expressions And Significances Of MSI2,DKK4,EPHX2 And JUP In Solid Pseudopapillary Tumor Of Pancreas

Objective: Solid pseudopapillary tumor of pancreas(SPT)is a kind of low-grade malignant tumor.For SPT,The pathogenesis of the disease and tissue origin is still poorly understood at present.SPT related specific tumor biomarkers are also lack.Isobaric tags for relative and absolute quantitation(i TRAQ)is a novel technique for proteome analysis.These studies were in order to understand the different protein expression between SPT tissue and normal pancreatic tissue by using i TRAQ technique,and to explore the pathogenesis and potential tumor biomarker of SPT.Methods: SPT tumor samples were obtained from nine patients suffering from SPT,each specimen including tumor tissues and normal pancreatic tissue was used as experimental specimen,and then we used i TRAQ technology integrated with liquid chromatography-tandem mass spectrometry(LC-MS/MS)analysis to identify differentially expressed proteins in SPT specimens.The studied proteins were blasted against KEGG genes(human)to retrieve their KEGG orthology identifications and were subsequently mapped to pathways in KEGGResults: A total of 1171 proteins with a threshold of a 1.5-fold change and a P value≤ 0.05 between SPTP tissue and matched normal pancreas tissue were identified for bioinformatics analysis.We observed that many endoplasmic reticulum-associated proteins were altered.Four representative proteins(Msi2,DKK4,EPHX2,JUP)were identified by MS with significant difference.Conclusions: This study established an i TRAQ technology integrated with LC-MS/MS approach for proteomic research of solid pseudopapillary tumor of pancreas.The endoplasmic reticulum stress may play an important role in SPTP tumorigenesis.Msi2,DKK4,EPHX2 and JUP could be considered as potential tumor markers.Objective: To evaluate whether the expression of Msi2,DKK4,EPHX2,and JUP have the potential to diagnosis solid pseudopapillary tumor of pancreas.Methods: Expression of Msi2,DKK4,EPHX2,and JUP were measured in 23 cases of SPT and 5 cases of non-tumoral tissues by tissue microarrays.Immunohistochemical staining intensity and staining area assessed.The positive results were divided into four grades,0,1+,2+,3+ staging which represented negative,mild positive,moderate positive and strong positive respectively.Results: Msi2 positive expression accounted for 91.3 %(21/23)in 23 cases of SPT tumor tissue samples,and the control group had 2 cases of positive expression(2/5),And the areas under the curve of the ROC curves was 0.870.The sensibility was 82.5% and specificity was 80.0 %.DKK4 positive expression accounted for 91.3 %(21/23)with AUC was 0.904.Its sensibility was 91.3 % and specificity was 60.0 %.EPHX2 positive expression accounted for 60.9 %(14/23)and JUP for 52.5 %(12/23),with AUC was 0.904.Its sensibility was 91.3 % and specificity was 60.0 %.And the areas under the curve of the ROC curves for EPHX2 and JUP were 0.930 and 0.922.The sensibility of EPHX2 was 91.3 % and the specificity of which was 80.0 %,the sensibility of JUP was 82.6 % and the specificity of which was 100.0 %Conclusions: For SPT,Msi2 and DKK4 were up-regulated,and other two were down-regulated,they appear to be valuable diagnostic markers in SPT.And DKK4 was a secreted protein.Follow-up studies will be further explored for the expression level of DKK4 in the peripheral blood of patients suffering SPT,to identify if DKK4 can work as potential peripheral blood screening biomarker for SPT.