title: 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 = 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 = 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 = 0.036) and exhibited a lower 5-year overall survival rate than did those lacking cpDNA mutations (5.6% vs. 31.5%, p = 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.
authors.affiliation: Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei City, Taiwan.|School of Medicine, National Yang-Ming University, Taipei City, Taiwan.
authors.forename: Wen-Liang
authors.initials: WL
authors.lastname: Fang
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei City, Taiwan.|Division of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei City, Taiwan.
authors.forename: Yuan-Tzu
authors.initials: YT
authors.lastname: Lan
authors.affiliation: Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei City, Taiwan.|School of Medicine, National Yang-Ming University, Taipei City, Taiwan.|Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei City, Taiwan.
authors.forename: Kuo-Hung
authors.initials: KH
authors.lastname: Huang
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei City, Taiwan.|Department of Radiology, Taipei Veterans General Hospital, Taipei City, Taiwan.
authors.forename: Chien-An
authors.initials: CA
authors.lastname: Liu
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei City, Taiwan.|Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei City, Taiwan.
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Hung
authors.affiliation: Genome Research Center, National Yang-Ming University, Taipei City, Taiwan.
authors.forename: Chien-Hsing
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei City, Taiwan.
authors.forename: Fang-Yu
authors.initials: FY
authors.lastname: Jhang
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei City, Taiwan.|Division of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei City, Taiwan.
authors.forename: Shih-Ching
authors.initials: SC
authors.lastname: Chang
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei City, Taiwan.|Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei City, Taiwan.
authors.forename: Ming-Huang
authors.initials: MH
authors.lastname: Chen
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei City, Taiwan.|Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei City, Taiwan.
authors.forename: Yee
authors.initials: Y
authors.lastname: Chao
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei City, Taiwan.|Institute of Biotechnology in Medicine, National Yang-Ming University, Taipei City, Taiwan.
authors.forename: Wen-Chang
authors.initials: WC
authors.lastname: Lin
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei City, Taiwan.|National Yang-Ming University Hospital, Yilan City, Taiwan.
authors.forename: Su-Shun
authors.initials: SS
authors.lastname: Lo
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei City, Taiwan.|Department of Pathology, Taipei Veterans General Hospital, Taipei City, Taiwan.
authors.forename: Anna
authors.initials: A
authors.lastname: Fen-Yau Li
authors.affiliation: Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei City, Taiwan.|School of Medicine, National Yang-Ming University, Taipei City, Taiwan.
authors.forename: Chew-Wun
authors.initials: CW
authors.lastname: Wu
authors.affiliation: Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei City, Taiwan.|Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei City, Taiwan.|Institute of Pharmacology, National Yang-Ming University, Taipei City, Taiwan.
authors.forename: Shih-Hwa
authors.initials: SH
authors.lastname: Chiou
authors.affiliation: Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei City, Taiwan.|School of Medicine, National Yang-Ming University, Taipei City, Taiwan.
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Shyr
mesh_terms: D000230:Adenocarcinoma / Q000097:blood* / Q000235:genetics / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000097:blood* / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000097:blood* / Q000235:genetics / Q000401:mortality; D016016:Proportional Hazards Models; D013274:Stomach Neoplasms / Q000097:blood* / Q000235:genetics / Q000401:mortality; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm
keywords: advanced gastric cancer; cpDNA; mutation; peritoneal recurrence; poor prognosis