Circulating Tumour Cells (CTCs) as Potential Biomarkers of Clinicopathological and Prognostic Significance in Gastric Cancer Patients: A Systematic Review and Meta-Analysis

Abstract

Background: Gastric cancer (GC) is a common highly recurrent malignant tumor that is associated with poor prognosis. Circulating tumor cells (CTCs) have drawn much attention because of their diagnostic value in diverse cancers, including GC. This study aimed to assess the relevance of CTCs in predicting the clinicopathological parameters and prognostic significance of GC. Methods: We systematically searched PubMed, Medline and Web of Science for relevant studies. Each database was searched from its date of inception through January 22, 2020. The odds ratios (ORs), hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated as effect values using the random-effects model. Results: In total, 52 articles that reported 68 studies comprising 4158 GC patients were included. The pooled results on TNM stage indicated that the III/IV group had a notably higher CTCs positivity rate than the I/II group (OR=2.73, 95% CI (1.95,3.82), I2=65%). The poorly differentiated group had a significantly higher CTCs positivity rate than the well/moderately differentiated group (overall: OR=1.91, 95% CI (0.77,4.71)), as well as the Lauren classification diffuse/hybrid type group and the intestinal group (overall: OR=1.77, 95% CI (0.70,4.44)). The bulk of analysis revealed that CTC positivity detected in GC patients was correlated with worse overall survival (OS) (HR =1.94, 95% CI (1.64,2.30), P≤0.001), progression-free survival (PFS) (HR =2.45, 95% CI (1.65,3.64), P≤0.001), and disease-free survival (DFS) (HR =2.78, 95% CI (1.89,4.10), P≤0.001). Then, we extracted data and analyzed the DCR of chemotherapy in patients with GC, and the pooled analysis demonstrated that the DCR of the CTC positivity was lower than that of the CTC negativity (RR =0.63, 95% CI (0.44,0.91))Conclusions: In conclusion, our study demonstrated that the CTCs positivity was correlated with the poor OS, PFS and DFS in GC patients and provided a scientific foundation for gastric cancer staging.