Diagnosis Accuracy and Prognostic Significance of the Dickkopf-1 Protein in Gastrointestinal Carcinomas: Systematic Review and Network Meta-analysis

Objective: To evaluate the diagnosis accuracy and prognostic significance of bio-marker dickkopf-1(DKK-1) protein in GIC, and also sub-type of hepatocellular carcinoma (HCC), pancreas carcinomas (PC), oesophageal carcinoma (EPC) and Adenocarcinoma of esophago-gastric junction (AEGJ), etc. Methods: Electronic databases were searched from inception to May 2020. Patients were diagnosed with gastrointestinal carcinomas, and provided data on the correlation between high and low DKK-1 expression and diagnosis or prognosis. Results: Forty-three publications involving 9318 participants were included in the network meta-analysis, with 31 of them providing data for diagnosis value and 18 records were eligible for providing prognosis value of DKK-1. DKK-1 has a moderate diagnostic value for overall GIC, HCC and PC. In addition, for the combined diagnosis value of DKK-1 +AFP, high diagnostic accuracy value could be determined in HCC and early HCC group, respectively. Whereas, diagnosis efficiency of DKK-1+CA19-9 was also better than that of DKK-1 alone with AUC value is above 0.95. For the prognosis meta-analysis of histopathological stratification, we found that EPC and AEGJ ranked the best for the histopathological stratification of prognosis from network meta-analysis. This systematic review protocol was registered with the PROSPERO registry (No.CRD42020167910). Conclusion: DKK-1 has good diagnostic accuracy, especially combination of DKK-1+AFP in HCC and DKK-1+CA19-9 in PC, whereas modest prognostic significant in GIC. Future head-to-head researches are warranted for DKK-1 expression in HCC and PC tissue.