Volume 138, Issue 12 pp. 2974-2983
Tumor Markers and Signatures

Clinical significance of circulating plasma DNA in gastric cancer

Wen-Liang Fang

Wen-Liang Fang

Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei City, Taiwan

School of Medicine, National Yang-Ming University, Taipei City, Taiwan

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Yuan-Tzu Lan

Yuan-Tzu Lan

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

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Kuo-Hung Huang

Kuo-Hung Huang

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

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Chien-An Liu

Chien-An Liu

School of Medicine, National Yang-Ming University, Taipei City, Taiwan

Department of Radiology, Taipei Veterans General Hospital, Taipei City, Taiwan

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Yi-Ping Hung

Yi-Ping Hung

School of Medicine, National Yang-Ming University, Taipei City, Taiwan

Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei City, Taiwan

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Chien-Hsing Lin

Chien-Hsing Lin

Genome Research Center, National Yang-Ming University, Taipei City, Taiwan

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Fang-Yu Jhang

Fang-Yu Jhang

Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei City, Taiwan

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Shih-Ching Chang

Corresponding Author

Shih-Ching Chang

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

S.-C.C. and Y.-M.S. contributed equally to this work.

Correspondence to: Shih-Ching Chang, Division of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd, Beitou District, Taipei City, Taiwan 11217, Tel: +886-2-28757544-110, Fax: +886-2-28757396, E-mail: [email protected] or Yi-Ming Shyr, Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd, Beitou District, Taipei City, Taiwan 11217, Tel: +886-2-28757536, Fax: +886-2-28757537, E-mail: [email protected]Search for more papers by this author
Ming-Huang Chen

Ming-Huang Chen

School of Medicine, National Yang-Ming University, Taipei City, Taiwan

Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei City, Taiwan

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Yee Chao

Yee Chao

School of Medicine, National Yang-Ming University, Taipei City, Taiwan

Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei City, Taiwan

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Wen-Chang Lin

Wen-Chang Lin

Institute of Biomedical Sciences, Academia Sinica, Taipei City, Taiwan

Institute of Biotechnology in Medicine, National Yang-Ming University, Taipei City, Taiwan

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Su-Shun Lo

Su-Shun Lo

School of Medicine, National Yang-Ming University, Taipei City, Taiwan

National Yang-Ming University Hospital, Yilan City, Taiwan

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Anna Fen-Yau Li

Anna Fen-Yau Li

School of Medicine, National Yang-Ming University, Taipei City, Taiwan

Department of Pathology, Taipei Veterans General Hospital, Taipei City, Taiwan

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Chew-Wun Wu

Chew-Wun Wu

Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei City, Taiwan

School of Medicine, National Yang-Ming University, Taipei City, Taiwan

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Shih-Hwa Chiou

Shih-Hwa Chiou

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

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Yi-Ming Shyr

Corresponding Author

Yi-Ming Shyr

Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei City, Taiwan

School of Medicine, National Yang-Ming University, Taipei City, Taiwan

S.-C.C. and Y.-M.S. contributed equally to this work.

Correspondence to: Shih-Ching Chang, Division of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd, Beitou District, Taipei City, Taiwan 11217, Tel: +886-2-28757544-110, Fax: +886-2-28757396, E-mail: [email protected] or Yi-Ming Shyr, Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd, Beitou District, Taipei City, Taiwan 11217, Tel: +886-2-28757536, Fax: +886-2-28757537, E-mail: [email protected]Search for more papers by this author
First published: 27 January 2016
Citations: 63

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.

Abstract

What's new?

Patients whose gastric cancer returns despite curative surgery tend to suffer poor prognosis. According to the authors of this study; however, it may be possible to catch recurrent disease before it reaches advanced stages using circulating plasma (cp) DNA, a blood-based biomarker. In advanced gastric cancer patients, cpDNA levels were associated with tumor recurrence and initial recurrence pattern, with high cpDNA levels signaling an increased likelihood of peritoneal recurrence versus locoregional or distant recurrence. Primary tumor mutations in cpDNA were linked to reductions in 5-year survival, suggesting that cpDNA mutational status can predict poor prognosis in late-stage disease.

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