Aberrant DNA methylation can be a potential genetic mechanism in non-small cell lung cancer (NSCLC). However, inconsistent findings existed among the recent association studies between cigarette smoking and gene methylation in lung cancer. The purpose of our meta-analysis was to evaluate the role of gene methylation in the smoking behavior of NSCLC patients. A total of 116 genes were obtained from 97 eligible publications in the current meta-analyses. Our results showed that 7 hypermethylated genes (including CDKN2A, RASSF1, MGMT, RARB, DAPK, WIF1 and FHIT) were significantly associated with the smoking behavior in NSCLC patients. The further population-based subgroup meta-analyses showed that the CDKN2A hypermethylation was significantly associated with cigarette smoking in Japanese, Chinese and Americans. In contrast, a significant association of RARB hypermethylation and smoking behavior was only detected in Chinese but not in Japanese. The genes with altered DNA methylation were likely to be potentially useful biomarkers in the early diagnosis of NSCLC.

BackgroundYKL-40 is also called chitinase-3-like-1 (CHI3L1) protein and may be a marker for asthma. The aims of the present study were to investigate whether serum YKL-40 levels are stable or decreased in patients with asthma after appropriate treatment and to evaluate the correlation of YKL-40 levels with lung function and asthma control test (ACT) results.MethodsA total of 103 asthmatic patients (mean age 33.1 ± 0.9 years) with diagnosed asthma were enrolled in our study. All patients underwent a detailed clinical examination and completed the ACT questionnaire, serum YKL-40 measurement, and spirometry before (visit 1) and 8 weeks after initiation of treatment (visit 2).ResultsAt the follow-up, the median serum YKL-40 level was significantly decreased compared to the levels at visit 1 (75.2 [55.8-86.8] ng/ml versus 54.5 [46.4-58.4] ng/ml, p < 0.001). The serum YKL-40 level was negatively correlated with %FEV1 (r = -0.37, p < 0.001) and ACT score (r = -0.26, p = 0.007) at visit 1. The change in serum YKL-40 levels between the visits was significantly correlated with changes in FEV1 (r = -0.28, p = 0.006) and ACT score (r = -0.22, p = 0.037). Patients with elevated YKL-40 levels had significantly greater corticosteroid use than patients with lower levels.ConclusionsYKL-40 was reduced in the serum of asthmatic patients after appropriate treatment, and the levels correlated with improvements in %FEV1 and ACT. High levels of serum YKL-40 may be refractory to current asthma treatments.Trial registrationChiCTR-OCC-13003316Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2466-15-1) contains supplementary material, which is available to authorized users.

No abstract

Changes of cytokines in bronchoalveolar lavage fluid (BALF) reflect immunologic reactions of the lung in pulmonary malignancies. Detection of biomarkers in BALF might serve as an important method for differential diagnosis of lung cancer. A total of 78 patients admitted into hospital with suspected lung cancer were included in our study. BALF samples were obtained from all patients, and were analyzed for TGF-β1, IL-6, and TNF-α using commercially available sandwich ELISA kits. The levels of TGF-β1 in BALF were significantly higher in patients with lung cancer compared with patients with benign diseases (P = 0.003). However, no significant difference of IL-6 (P = 0.61) or TNF-α (P = 0.72) in BALF was observed between malignant and nonmalignant groups. With a cut-off value of 10.85 pg/ml, TGF-β1 showed a sensitivity of 62.2%, and a specificity of 60.6%, in predicting the malignant nature of pulmonary disease. Our data suggest that TGF-β1 in BALF might be a valuable biomarker for lung cancer. However, measurement of IL-6 or TNF-α in BALF has poor diagnostic value in lung cancer.

Oxidative stress induced by tobacco smoking is one of the main causes of DNA damage and is known to be involved in various cancers. Smoking is the leading cause of lung cancer, while the role of cigarette smoke-induced oxidative DNA damage response during lung carcinogenesis is largely unknown. In this study, we investigated oxidative DNA damage response levels in smoking and nonsmoking patients with lung cancer, and evaluated the potential diagnostic value of 8-OHdG for lung cancer. We observed a higher level of 8-OHdG expression and secretion in airways of lung cancer patients than that of noncancer controls. 8-OHdG expression was associated with the TNM stages. Additionally, cigarette smoke-induced oxidative DNA damage response was observed in bronchial epithelial cells in vitro and in vivo. A statistical significance correlation was found between the levels of 8-OHdG and smoking index. With a cut-off value of 2.86 ng/ml, 8-OHdG showed a sensitivity and specificity of 70.0% and 73.7%, respectively, to identify a patient with lung cancer. These findings not only underscore the importance of smoking in oxidative DNA damage response of lung cancer patients, but also suggest 8-OHdG as a potential diagnostic biomarker for lung cancer.