Diagnostic and prognostic value of circulating tumor DNA in gastric cancer: a meta-analysis

Abstract

BackgroundCirculating tumor DNA (ctDNA) has offered a minimally invasive approach for detection and measurement of gastric cancer (GC). However, its diagnostic and prognostic value in gastric cancer still remains unclear.ResultsA total of 16 studies comprising 1193 GC patients met our inclusion criteria. The pooled sensitivity and specificity were 0.62 (95% confidence intervals (CI) 0.59−0.65) and 0.95 (95% CI 0.93–0.96), respectively. The AUSROC (area under SROC) curve was 0.94 (95% CI 0.89–0.98). The results showed that the presence of certain ctDNA markers was associated with larger tumor size (OR: 0.26, 95% CI 0.11–0.61, p = 0.002), TNM stage (I + II/III + IV, OR: 0.11, 95% CI 0.07−0.17, p = 0.000), as well as H. pylori infection. (H.p negative/H.p positive, OR: 0.57, 95% CI 0.36–0.91, p = 0.018). Moreover, there was also a significant association between the presence of ctDNA and worse overall survival (HR 1.77, 95% CI 1.38−2.28, p < 0.001), as well as disease-free survival (HR 4.36, 95% CI 3.08−6.16, p < 0.001).Materials and MethodsPubmed, Embase, Cochrane Library and Web of Science databases were searched for relating literature published up until November 30, 2016. Diagnostic accuracy variables were pooled by the Meta-Disc software. Engauge Digitizer and Stata software were applied for prognostic data extraction and analysis.ConclusionsOur meta-analysis indicates the detection of certain ctDNA targets is significantly associated with poor prognosis of GC patients, with high specificity and relatively moderate sensitivity.

Clinical Application of Circulating Tumor DNA in the Genetic Analysis of Patients with Advanced GIST

“…a positive correlation between ctDNA detection and the total number of tumor cells in the primary tumor in the early stage of pancreatic cancer. Gao and colleagues (19) showed that the presence of ctDNA was associated with larger tumor size, TNM stage, and Helicobacter pylori infection in gastric cancer. Similarly, we demonstrated that the positive rate of ctDNA detection was positively correlated with tumor size and Ki-67 in advanced GIST patients.…”

Circulating tumour cells and DNA as liquid biopsies in gastrointestinal cancer

“…CTCs and ctDNA may be of prognostic value in several gastrointestinal cancers, where the biggest impact may be their detection before therapeutic intervention. As a cancer (or minimal residual disease) evolves with time and treatment, selection pressure from surgery, chemotherapy or radiotherapy, or tumoricidal immunity could stimulate the expansion of tumour subclones ( Fig .…”

“…They further demonstrated that ctDNA detection after therapy predicted shorter recurrence‐free survival both in patients who did not receive chemotherapy and in those who did. A meta‐analysis of mixed‐stage gastric cancer demonstrated significantly shorter disease‐free and overall survival in patients in whom ctDNA was detected. This prognostic value has been confirmed for localized gastric cancer in at least one separate study.…”

Diagnostic value of circulating tumor DNA as an effective biomarker in cervical cancer: a meta-analysis

“…In pathological analysis, traditional surgical specimens are used as the gold standard for obtaining fundamental information for clinical decision-making. However, obtaining such specimen directly from tumors is an invasive procedure and can delay the observation of tumor dynamic changes after treatment [39]. Cancers are known to shed tumor cell DNA into the blood stream [34], and examining the levels and mutations in ctDNA can provide almost realtime information regarding tumor status.…”

“…Many previous meta-analyses have reported that the diagnostic accuracy of quantitative analysis of ctDNA is superior to conventional biomarkers for the diagnosis of several cancers, including ovarian cancer [22], lung cancer [45], gastric cancer [39], and colon cancer [46].…”