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.
Highlights
Gastric cancer (GC) remains the fifth most common cancer and the third leading cause of cancer-related death worldwide [1, 2]
Serum-based protein biomarkers such as carcinoembryonic antigen (CEA) [6], carcinoma antigen 125 (CA-125) [7], carcinoma antigen 724 (CA-724) [8], and carcinoma antigen 19-9 have commonly been used for GC patient management, they are plagued by limited diagnostic, and prognostic capacity [9]
Studies were included in the analysis if they met the following criteria: [1] they enrolled patients with pathologically confirmed gastric or gastroesophageal junction adenocarcinoma; [2] they reported GC patient survival data stratified by Circulating tumor cells (CTCs)/circulating tumor deoxyribonucleic acid (ctDNA)/circulating miRNA status; [3] they provided sufficient data for determining or calculating a hazard ratio (HR) and 95% confidence interval (95%CI); and [4] they enrolled patients who did not overlap with patients included in other eligible studies
Summary
Gastric cancer (GC) remains the fifth most common cancer and the third leading cause of cancer-related death worldwide [1, 2]. Circulating tumor cells (CTCs) and cell-free nucleic acids (cfNAs), known as “liquid biopsies,” are detectable biomarkers across tumor types and represent attractive putative targets in GC [10,11,12,13]. The potential advantages of liquid biopsy have been demonstrated in the management of breast cancer, colorectal cancer, and prostate cancer [14,15,16], but evidence of their effectiveness in GC management is limited and controversial. 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
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