| Part 1 Detection of plasma exosomal Cripto-1 and its diagnostic and prognostic value in gastric cancerBackground:Gastric cancer(GC)is a common malignant tumor,the poor prognosis of GC resulted from late detection,aggressive characteristics and poor response to available therapies.Exosomes can promote the communication between cells by transferring functional vectors such as protein,RNA and DNA in many biological processes.As a diagnostic biomarker and individualized treatment model,it has broad application prospects.However,there is no report about the expression of Cripto-1 in exosomes and its clinical value in gastric cancer.Therefore,this study explored the abnormal expression of exosomal Cripto-1 in the plasma of patients with gastric cancer and its value in the diagnosis and prognosis of gastric cancer.Methods:1.The exosomes of SGC7901 and BGC823 were extracted by ultracentrifugation and identified by electron microscopy and western blot.The expression of cripto-1 in GC cell lines and releasing exosomes was observed by western blot.2.The exo-ELISA method was established to detect the expression levels of the plasma exosomal cripto-1 in 118 GC patients,62 non-atrophic gastritis patients,26 gastric polyps,62 atrophic gastritis patients and 60 healthy controls.3.The receiver operating characteristic(ROC)curve was used to evaluate the diagnostic efficacy of plasma exosomal cripto-1,CA72-4 and CEA for GC.4.Kaplan-meier curves were drawn to analyze the correlation between the expression level of plasma exosomal cripto-1 and the 5-year survival rate of GC patients.5.COX multivariate regression model was established to analyze the prognostic value of plasma exosomal cripto-1 in GC.Results:1.The level of plasma exosomal Cripto-1 was significantly higher in GC group than the other four groups(P<0.05).There was a positive correlation between the level of plasma exosomal Cripto-1 and the age of patients and the depth of tumor invasion(P<0.05).2.The ROC curve showed that the diagnostic efficiency of the area under the Cripto-1 curve(AUC=0.763)of plasma exosomes for GC was higher than that of CEA(AUC=0.621)and CA72-4(AUC=0.641).When the optimal cut-off value(0.765)was used,the sensitivity and specificity of exosomal Cripto-1 in the diagnosis of gastric cancer were 80.5%and 69.1%,respectively(P<0.001).3.Kaplan Meier analysis showed that the 5-year survival rate of gastric cancer patients was negatively correlated with the high level of plasma exosomal Cripto-1(P<0.05).In addition,the 5-year OS of patients with high CEA expression was significantly lower than that of patients with low CEA expression(P<0.05),and the content of CA72-4 was not statistically correlated with the 5-year OS of gastric cancer patients(P>0.05).4.Cox multivariate regression model analysis showed that tumor lymph node metastasis,high level of serum CEA and high level of plasma exosomal Cripto-1 were the risk prognostic factors of gastric cancerConclusion:In this study,we successfully establish a method for the detection of human plasma exosomal Cripto-1.The diagnostic value of plasma exsomal Cripto-1 for GC is higher than traditional tumor markers,CEA and CA72-4.It has certain guiding significance for the prognosis of patients with GC.Part 2 Cripto-1 as a prognostic predictor of malignancies:a systematic review and meta-analysisBackground:The studys show that Cripto-1 plays an important role in tumor development.It has been reported to be highly expressed in lung cancer,colorectal cancer,breast cancer,GC,pancreatic cancer,bladder cancer,renal cancer,liver cancer and other cancer tissues,and is associated with prognosis.The aim of this paper is to evaluate the correlation between the expression level of Cripto-1 and the prognosis of cancer patients through systematic review and meta-analysis.Methods:The literature retrieval was carried out by two independent reviewers through electronic databases including PubMed,Embase,and Web of Science.The literature published between January 1994 and September 2019 was considered for the analysis.2.To establish inclusion and exclusion criteria to screen literature,overall survival(OS)as the main evaluation index,progression-free survival(PFS),disease-free survival(DFS)and recurrence-free survival(RFS)as the secondary evaluation index.3.A rigorous review table was used to assess the quality of the literature included.4.The risk ratio(HR)and the associated 95%confidence interval(95%CI)were used to calculate the combined effect.All statistical analysis was performed using Stata 12.0.Results:A total of 11 articles and 2358 participants were ultimately included in the meta-analysis.Statistical analysis showed that the overall survival time of patients with high expression of Cripto-1 was lower than the patients with low expression(HR=2.25,95%CI:1.67-3.03).The analysis of the relationship between the expression level of Cripto-1 and the progression-free survival(PFS)showed that the high expression level of Cripto-1 indicated the rapid progress of cancer.In addition,patients with high level of Cripto-1 were more likely to have lymph node metastasis and distant metastasis than those with low expression of Cripto-1.The risk ratio(HR)of the combination was 2.22(95%CI:1.47-3.36)and 2.48(95%CI:1.52-4.04),respectively.Conclusion:This meta analysis shows that the overall survival rate and progression free survival of patients with high-level expression of Cripto-1 are shorter than those of patients with low expression of Cripto-1,indicating that Cripto-1 is closely related?prognosis evaluation,and provide guidance for the prognosis evaluation of cancer patients in the future. |
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