| Objection:Gastric cancer is one of the most common malignancy tumors and the mainleading cause of cancer-related death in the world. Based on the data of IARC, newmorbidity of gastric cancer in the world is952,000people (excluded people didn’t seedoctors) in2012, which408,000was Chinese (42.6%); the mortality rate of gastriccancer in the world is10.2in100,000people in2012, which325,000was Chinese,mortality rate was21.9in100,000. Therefore, studying the molecular biologicalmechanisms of tumorigenesis and prognosis of gastric cancer, finding the biologicalmarkers of prognosis and predicting the prognosis of gastric cancers are the researchdirection of gastrointestinal surgeons.Methods:In prior study, we have screened the signaling proteins associated with gastriccancer using PPA analysis,27proteins was found differently expressed betweengastric cancer tissue and normal tissues, in which9proteins was up-regulated ingastric caners. Therefore, the study was to verify the expression of the9proteins.Tissue Microarray analysis (TMA) were used to assess the expression of9proteins ina total of121gastric cancers and30normal tissues. To identify the proteins associatedwith other important clinicopathologic characteristics, such as tumor size, histologicaldifferentiation and vascular/lymphatic invasion, X2analysis and Fisher’s exact testwere performed. This study also tested these differentially expressed proteins usingclustering analysis and performed proteomic-wide expression analysis using IngenuityPathway Analysis (IPA) software to investigate the significant proteins’ expression insignaling network of gastric cancer. To identify the survival feature proteins of gastriccancer, we performed a survival feature analysis using clustering analysis and survivalanalysis. For predicting the prognosis of gastric cancer patients, we performed factor analysis using differentially expressed proteins and clinicopathologic characteristicsassociated with survival and established models to predict survival of gastric cancerpatients.Results:In our study we found that8proteins in9were differentially expressed betweengastric cancer tissues and normal tissues using TMA analysis. The8differentlyexpressed proteins existed in different tumor size, histological differentiation andvascular/lymphatic invasion and could be the developmental, tumor staging andprognostic molecular markers. Based on the differently expressed proteins, IPAsystem proposed the signaling transduction network of gastric cancer. IPA systemsanalysis results showed that these proteins were closely related with cell death andsurvival, DNA duplication, Restructuring and repair, cell circle, cellular developmentand cellular growth and proliferation in addition to cancer, metabolic disease,neurological disease, Psychological disorders and hematological disease, the topcanonical pathways were molecular mechanisms of cancer, HER-2signaling in breastcancer, glioma signaling HGF signaling and UVB-induced MAPK signaling. Theupstream regulative proteins may be the therapy target of gastric cancer. After clustinganalysis, we found several differences between Clusters; further survival analysisshowed that5proteins (CDK2，AKT1，XIAP，Notch4and p-PKC/β2) divided allthe patients into2clusters,5-Proteins Clusters, age, tumor size and vascular/lymphatic invasion were independent risk factors of gastric cancer. Factor analysisshowed Factor1(Proteins Factor), Factor2(Pathological Factor), Factor3(ClinicalFactor) and Factor4(Histological Classification Factor) were independent survivalrisk factors of gastric cancer, The4models consisted of4factors could also predictthe prognosis of gastric cancer patients.Conclusion:Our study focus on the9signaling pathway proteins found in prior study, weperformed TMA analysis on the gastric cancers and normal tissues and to study thefunction of protein signal transduction pathway in gastric cancer in tumor cellsdevelopment, movement, proliferation/growth and apoptosis.8in9proteins weredifferently expressed; the dysregulation of signaling proteins were correlated withtumor size, histological differentiation and vascular/lymphatic invasion, these proteinscould be the developmental and prognostic molecular markers. After survival feature analysis of the8protein,5proteins could divided the all patients into two groupswhich were different in lymph node metastasis and TNM staging and5-ProteinClusting were independent risk factors of gastric cancer. Specially, factor analysisshowed Factor1(Proteins Factor), Factor2(Pathological Factor), Factor3(ClinicalFactor) and Factor4(Histological Classification Factor) were independent survivalrisk factors of gastric cancer and established four effective detection systems forpredicting the prognosis of gastric cancer patients. |
PDF Full Text Request