2558-2564-Circulating DNA for detection of gastric cancer

persons and mortality rate of 498.0/1000 persons, which is second only to that of lung cancer, ranking the second most malignant cancer and the most malignant tumor of the gastrointestinal tract. High incidence of GC is observed in East China, Southwest China, North China and Central China. In these areas, morbidity and mortality are two times higher in males than in females, and higher in rural areas than in urban areas2. Due to non-significant symptoms being present at the early stage of GC, over half of the patients have missed the opportunity for radical surgery at diagnosis. For these patients, chemotherapy is the most common option of treatment. Unfortunately, the efficacy of chemotherapy is often limited due to congenital and acquired drug resistance. Despite the decreasing incidence of GC in China, the 5-year survival rate is still less than 30%. Therefore, early diagnosis and therapeutic evaluation of GC is urgent an issue to be resolved. In this regard, researchers have been searching for ideal tumor markers, and increasing attentions have been drawn to the prospect of using circulating DNA in clinical diagnosis and treatment of malignant carcinomas. Circulating cell-free DNA (cfDNA) is cell-free extracellular DNA in the forms of single-stranded (ss) or double-stranded (ds) DNA, or a mixture of ss DNA and ds DNA, presenting in the blood (the plasma or the serum), synovial fluid and other body fluid of animal and human. In 1948, Mandel and Metais3 detected cfDNA in human blood for the first time. However, the knowledge of cfDNA was limited to its relationship with autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis and glomerulonephritis, as well as its association with chronic inflammation, such as pancreatitis, inflammatory bowel disease and hepatitis4,5. Until 1977, Leon et al6 showed that circulating plasma DNA is significantly increased in cancer patients and demonstrated the utility of assessing DNA levels in peripheral blood in the therapeutic evaluation and prognostic prediction. These findings were subsequently verified by many other investigations7,8. Moreover, Abstract. – OBJECTIVE: Gastric cancer (GC) is one of the most common malignant tumors worldwide, particularly, prevalent in China. Despite the decreasing incidence of GC in China, the 5-year survival rate is still not over 30% yet. Therefore, early diagnosis and therapeutic outcome evaluation of GC remains as the issue to be resolved in a clinical setting. MATERIALS AND METHODS: Recent studies have found the presence of a certain amount of circulating DNA in the peripheral blood of patients with malignant tumor and shown that these free DNA bear tumor-specific genetic information. The circulating DNA detection includes quantitative and qualitative methods and analysis. Combined monitoring of changes in circulating DNA levels and aberrant alteration of relevant tumor genes is likely to provide comprehensive real-time information to patients. RESULTS: Under normal conditions, oncogene presents in the form of proto-oncogene such as K-ras, which is in non-carcinogenic status under the influence of tumor suppressor gene. When tumor suppressor gene is damaged or mutated of oncogene itself is induced for instance P53, oncogene is then activated and induces tumorigenesis. However, compared to gene mutation detection, the detection of DNA methylation is relatively more well-developed and stable. CONCLUSIONS: This article reviews the current status of the research on circulating DNA in the diagnosis, assessment of response to therapy and prognostic evaluation in GC. In addition, the advantage, current issue and prospect of using circulating DNA as tumor marker are also analyzed.