Serum glycine dehydrogenase is associated with increased risk of lung cancer and promotes malignant transformation by regulating DNA methyltransferases expression.

Identification of novel risk factors that are critical to the initiation of lung cancer will be key for its prevention. Recently, it has been reported that glycine dehydrogenase (GLDC) can drive the formation of lung cancer initiating cells. However, there have been no perspective studies on the association between circulating GLDC and lung cancer until now. To identify whether serum GLDC is a risk factor for lung cancer, the present study conducted a nested case­control study within a Chinese cohort. Using ELISAs, serum GLDC was measured in 300 case subjects, who were subsequently diagnosed with lung cancer during follow­up, and in 600 matched healthy controls. The results revealed that serum GLDC was associated with increased lung cancer risk [odds ratio=1.48; 95% confidence intervals (1.01­2.04)]. Spearman correlation was employed to analyze the associations between age, body mass index, years of smoking and the serum concentration of GLDC. It was demonstrated that years of smoking was associated with serum GLDC (spearman's correlation, ρ=0.81) in patients with lung cancer. However, the association was attenuated in the serum of matched controls (ρ=0.48). In addition, overexpression of GLDC protein contributed to malignant transformation and inhibited microRNA (miR)­29 family expression in normal human bronchial epithelial (NHBE) cells. Aberrant methylation of tumor suppressive gene (TSG) is an early event in the development of lung cancer, which is controlled by DNA methyltransferases (DNMTs). The present study demonstrated that GLDC promoted the expression of DNMT proteins; however, the miR­29 family inhibited their expression in NHBE cells. Thus, it was concluded that elevated serum GLDC may increase lung cancer risk, and that smoking, GLDC, the miR­29 family and DNMT signaling pathways may serve an important role in early malignant transformation during the development of lung cancer.

[Changes of NO2-/NO3- and nitration tyrosine concentrations in induced sputum of silicosis patients].

OBJECTIVE: To analyze the change in nitration tyrosine, NO(2)(-)/NO(3)(-)level in induced sputum of silicosis patients and dust exposure workers and to evaluate the approach and feasibility of nitric oxide (NO) metabolites as early detection indicators of silicosis. METHODS: Nitration tyrosine, NO(2)(-)/NO(3)(-)concentration in induced sputum of 80 dust exposure workers, 84 silicosis patients, 30 logistic personnel with no history of exposure to silica dust were determined and the relationship among Nitration tyrosine, NO(2)(-)/NO(3)(-)level and dust exposure years as well as pulmonary function tests were analyzed. RESULTS: NO(2)(-)/NO(3)(-)level among exposed group [60.30 (46.58) micromol/l] was significantly higher than the control group [36.90 (22.28) micromol/l], (P < 0.05), and the level of NO(2)(-)/NO(3)(-)among the cases [79.65 (89.10) micromol/l] was significantly higher than exposed group as well as the control group (P < 0.05). Compared with control, the level of nitration tyrosine in exposed group [3.51 (0.46) nmol/l] and the cases [3.48 (0.49) nmol/l] was significantly higher (P < 0.05). NO(2)(-)/NO(3)(-)level and dust exposure years were positively correlated (r = 0.3733 and 0.3830 respectively P < 0.05); NO(2)(-)/NO(3)(-)level and pulmonary function tests (FVC%, FEV1.0%, PEF%, MEF25%, MEF50%) were negatively correlated (r = 0.1540, 0.1723, 0.1535, 0.1485, 0.1643 respectively, P < 0.05). There was no correlation between nitration tyrosine and dust exposure years (P > 0.05), no correlation between nitration tyrosine and pulmonary function test (P > 0.05). CONCLUSION: The level of NO(2)(-)/NO(3)(-)level in induced sputum has a positive correlation with exposure to dust, suggesting that there will be a certain feasibility of the NO(2)(-)/NO(3)(-)as indicators of early detection of silicosis.