Clinical significance of circulating plasma DNA in gastric cancer

Abstract

With the progression of molecular techniques, the detection of circulating plasma DNA (cpDNA) is clinically feasible. However, the role of the cpDNA levels in gastric cancer is not well understood. This study assessed the mutational profile in primary tumors and clarified the clinical utility of quantitative and qualitative cpDNA alterations in 277 patients with advanced gastric cancer. The concentrations of cpDNA were measured by TaqMan qPCR, and 68 mutations in 8 genes were studied for cpDNA mutations. The median cpDNA concentrations in patients with stages I, II, and III gastric cancer were 3979, 3390 and 4278 copies/mL, respectively, and increased to 11,380 copies/mL in patients with Stage IV gastric cancer (p < 0.001). Among the 35 patients harboring cpDNA mutations, Stage IV patients (100%) were more likely to display high cpDNA levels than were Stage I (33.3%), II (75%) and III patients (66.7%) (p 5 0.037). Patients displaying high cpDNA levels were more likely to experience peritoneal recurrence and exhibited significantly lower 5-year overall survival rates (39.2% vs. 45.8%, p 5 0.039) than did patients displaying low cpDNA levels. Only for late stage (Stages III or IV) gastric cancer, patients harboring cpDNA mutations were more likely to experience vascular invasion (20% vs. 2.4%, p 5 0.036) and exhibited a lower 5-year overall survival rate than did those lacking cpDNA mutations (5.6% vs. 31.5%, p 5 0.028). High cpDNA levels are associated with peritoneal recurrence and poor prognosis in patients with advanced gastric cancer; harboring cpDNA mutations is associated with poor prognosis among patients with late stage gastric cancer.Although the worldwide incidence of gastric cancer has been declining, it remains the 5th most common cancer, accounting for 723,000 deaths worldwide in 2012.1 Surgical resection and lymphadenectomy are the standard of care for curing gastric cancer, and the tumor stage provides important prognostic insight. 2Peritoneal recurrence is the most common pattern of gastric cancer recurrence after curative surgery and is often

Identification of DNA mutations in gastric washes from gastric adenocarcinoma patients: Possible implications for liquid biopsies and patient follow‐up

“…In agreement with the literature, tumor‐derived mutation frequencies in our cohort were higher in patients with stages III and IV . The detection rate of ctDNA is expected to be increased in patients with metastatic or advanced disease (stages III and IV), due to the higher tumor mass and number of circulating tumor cells, tumor necrosis and apoptosis in such stages . In this sense, the investigation of potential biomarkers in the GW, especially in patients with early‐stage GAC, is very important in the context of liquid biopsy and early diagnosis, as the more intimate contact of this biofluid with gastric tumor lesions may facilitate ctDNA detection.…”

“…Among these, TP53 has been reported as one of the most frequently mutated genes in GAC, with frequencies varying from 13% to 70% . The mutational rate of TP53 found in this study (32.6%) is similar to previous findings (38%, n = 138), (33%, n = 251) and (38.7%, n = 106), but discrepant to others, which found mutation rates of 50% ( n = 295), 59% ( n = 49) or 13% ( n = 277) . In GAC, TP53 mutations appear to play an important role in the early stages of carcinogenesis and have also been found in potentially malignant lesions, such as intestinal metaplasia, where the number of mutations seems to accumulate as the disease progresses .…”

“…Some studies have been performed evaluating cell free DNA in plasma/serum of GAC patients . In our study, 40% of the patients had the same tumor‐biopsy TP53 mutations found in their plasma samples.…”

Preoperative Circulating Tumor DNA in Patients with Peritoneal Carcinomatosis is an Independent Predictor of Progression-Free Survival

“…26 Detectable ctDNA alterations also vary by stage of disease, and patients with peritoneal metastases are thought to have higher levels than those with localized disease. 27 The two most common alterations - in TP53 and KRAS - are typical of gastrointestinal malignancies and represent the most commonly mutated genes in human cancer. 28 Furthermore, inactivation of TP53 is typically a truncal driver event, and shed from all tumor cells.…”

Clinical relevance of cell-free DNA in gastrointestinal tract malignancy

“…In gastric cancer, patients with high cfDNA levels were more likely to experience peritoneal recurrence and exhibited significantly lower 5-year overall survival rates than patients with low cfDNA levels [12]. …”