| BackgroundGastrointestinal malignancy is one of the most common causes of cancer-related death worldwide, and China is one of the countries with a high incidence of the disease. Development of efficient diagnostic methods to enable their early detection plays an essential role in increasing the survival rate of patients with these diseases. Although endoscopy is considered the most sensitive screening tool for gastrointestinal malignancies, its use is limited due to its considerable cost and risk, and patients'lack of acceptance of the invasive procedure. In China, a developing country with a huge population, endoscopy is not suitable for large screening programs. Therefore, reliable noninvasive test, preferably blood test, for screening and diagnostic purposes are obviously needed. Plasma DNA, also known as circulating cell-free DNA, is a kind of deoxyribonucleic acid existing in the bloodstream but out of blood cells. In recent years, many studies demonstrated that increased concentrations of cell-free DNA in plasma or serum had been found in patients suffering from different types of cancer. However, the quantification and clinical-pathological characteristics of plasma DNA in gastrointestinal malignancies have not yet been investigated in a systemic research.ObjectiveThe aim of this study was to quantify the cell-free DNA in plasma samples from patients with different types of gastrointestinal malignancies and to attempt to correlate the resultants with the clinical-pathological parameters.MethodsA total of 177 patients suffer from gastrointestinal malignancies and 250 healthy controls from the First Affiliated Hospital of Nanjing Medical University were enrolled in the study. DNA was extracted from plasma samples of these patients and healthy controls by using the plasma DNA magnetic bead extraction kit. The quantity of plasma DNA was determined by using duplex real-time quantitative PCR with internal control. Carcinoembryonic antigen (CEA) was determined by radioimmunoassay. The performance of the test was evaluated with a ROC curve. The relationship between the DNA concentration and main demographic, clinical and pathological variables was examined.ResultsThe median concentration of the plasma DNA in the healthy controls was 18.2 ng/ml. A significant difference was seen in the median plasma DNA between different types of gastrointestinal malignancies and the healthy controls: esophageal cancer, Median (ME): 42.2 ng/ml, Interquartile range (IQR): 27.0~63.6 ng/ml, P< 0.001; gastric cardiac carcinoma, ME: 31.9 ng/ml, IQR: 19.9~52.9 ng/ml, P=0.003; gastric cancer, ME: 106.4 ng/ml, IQR: 73.2~141.6 ng/ml, P< 0.001; colon cancer, ME: 49.9 ng/ml, IQR: 26.6~73.2 ng/ml, P< 0.001; and rectal cancer, ME: 40.8 ng/ml, IQR: 27.1~55.5 ng/ml, P< 0.001. Plasma DNA was significantly associated with pathological stage and grading in esophageal cancer and colon cancer. And in rectal cancer, the concentration of plasma DNA correlated with pathological stage and tumor size (P<0.05). No association was observed between plasma DNA values and the various clinical-pathological parameters in gastric cardiac carcinoma and gastric cancer. But a trend was found that plasma DNA increased in advanced stage and poor differentiation. The areas under the ROC curves (AUC ROC) assessing plasma DNA concentration were significantly larger than serum CEA for the five types of cancers. Plasma DNA was more sensitive than CEA in detecting gastrointestinal malignancies. In gastric cancer, compared with serum CEA, plasma DNA had the highest diagnostic efficiency (sensitivity 96.3%, specificity 100%, AUC ROC = 0.990).ConclusionPlasma DNA values are significantly higher in patients with gastrointestinal malignant neoplasm than the healthy controls, which have practical implications in screening programs and monitoring progression of gastrointestinal malignancies, especially in gastric cancer. |
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