Association Between Liquid Biopsy and Prognosis of Gastric Cancer Patients: A Systematic Review and Meta-Analysis

Yunhe Gao, Hongqing Xi, Bo Wei, Jianxin Cui, Kecheng Zhang, Hua Li, Aizhen Cai, Weishen Shen, Jiyang Li, Rafael Rosell, Joseph Chao, Tianhui Chen, Samuel Klempner, Zhi Qiao, Lin Chen, Yunhe Gao, Hongqing Xi, Bo Wei, Jianxin Cui, Kecheng Zhang, Hua Li, Aizhen Cai, Weishen Shen, Jiyang Li, Rafael Rosell, Joseph Chao, Tianhui Chen, Samuel Klempner, Zhi Qiao, Lin Chen

Abstract

Background: Reports regarding liquid biopsy and gastric cancer (GC) have emerged rapidly in recent decades, yet their prognostic value still remains controversial. This study was aimed to assess the impact of liquid biopsy, including circulating tumor cells (CTCs) and cell-free nucleic acids, on GC patients' prognosis. Methods: PubMed, Medline, EMBASE, and ClinicalTrial.gov databases were searched for studies that report GC patient survival data stratified by CTC/circulating tumor DNA (ctDNA)/circulating miRNAs' status. The hazard ratios (HRs) and their 95% confidence intervals (CIs) for patients' overall survival (OS) and disease-free survival (DFS)/progression-free survival (PFS) were recorded or calculated depending on circulating target status. Results: We initially identified 4,221 studies, from which 43 were eligible for further analysis, comprising 3,814 GC patients. Pooled analyses showed that detection of certain CTCs, ctDNA, and circulating miRNA was associated with poorer OS (CTCs: HR = 1.84, 95%CI 1.50-2.26, p < 0.001; ctDNA: HR = 1.78, 95%CI 1.36-2.34, p < 0.001; circulating miRNA: HR = 1.74, 95%CI 1.13-2.69, p < 0.001) and DFS/PFS (CTCs: HR = 3.39, 95%CI 2.21-5.20, p < 0.001; ctDNA: HR = 2.38, 95%CI 1.31-4.32, p = 0.004; circulating miRNA: HR = 3.30, 95%CI 2.39-4.55, p < 0.001) of GC patients, regardless of disease stage and time point at which sample is taken (at baseline or post-treatment). Conclusions: The presence of CTCs and/or cellular components identifies a group of GC with poorer prognosis. Among circulating markers, CTCs demonstrated a stronger and more stable predictive value for late-stage disease and among Mongolian populations with GC. Less data are available for ctDNA and miRNA; however, their presence may also reflect aggressive biology and warrants further prospective study.

Keywords: circulating mRNA; circulating tumor DNA; circulating tumor cells; gastric cancer; liquid biopsy; prognosis.

Copyright © 2019 Gao, Xi, Wei, Cui, Zhang, Li, Cai, Shen, Li, Rosell, Chao, Chen, Klempner, Qiao and Chen.

Figures

Figure 1
Figure 1
Flowchart of enrolled studies investigating the association of liquid biopsy and gastric cancer patients' prognosis.
Figure 2
Figure 2
Forest plots of HRs for OS and DFS/PFS of GC patients, by CTC status. (A) Overall analysis of HR for OS of GC patients. (B) Subgroup analysis of HR for OS of the GC patients by detection targets. (C) Overall analysis of HR for DFS/PFS of GC patients. (D) Subgroup analysis of HR for DFS/PFS of GC patients by detection targets. HRs, hazard ratios; OS, overall survival; DFS, disease-free survival; PFS, progression-free survival; GC, gastric cancer; CTC, circulating tumor cell.
Figure 3
Figure 3
Forest plots of HRs for (A) OS and (B) DFS/PFS of GC patients, based on detection of circulating tumor DNA status. HRs, hazard ratios; OS, overall survival; DFS, disease-free survival; PFS, progression-free survival; GC, gastric cancer.
Figure 4
Figure 4
Forest plots of HRs for (A) OS and (B) DFS/PFS of GC patients, based on detection of circulating miRNA status. HRs, hazard ratios; OS, overall survival; DFS, disease-free survival; PFS, progression-free survival; GC, gastric cancer.

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