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

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

JOURNAL=Frontiers in Oncology

VOLUME=9

YEAR=2019

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2019.01222

DOI=10.3389/fonc.2019.01222

ISSN=2234-943X

ABSTRACT=<p><bold>Background:</bold> 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.</p><p><bold>Methods:</bold> 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.</p><p><bold>Results:</bold> 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, <italic>p</italic> &lt; 0.001; ctDNA: HR = 1.78, 95%CI 1.36–2.34, <italic>p</italic> &lt; 0.001; circulating miRNA: HR = 1.74, 95%CI 1.13–2.69, <italic>p</italic> &lt; 0.001) and DFS/PFS (CTCs: HR = 3.39, 95%CI 2.21–5.20, <italic>p</italic> &lt; 0.001; ctDNA: HR = 2.38, 95%CI 1.31–4.32, <italic>p</italic> = 0.004; circulating miRNA: HR = 3.30, 95%CI 2.39–4.55, <italic>p</italic> &lt; 0.001) of GC patients, regardless of disease stage and time point at which sample is taken (at baseline or post-treatment).</p><p><bold>Conclusions:</bold> 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.</p>