Zaichun Deng

Meta-analyses of gene methylation and smoking behavior in non-small cell lung cancer patients

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.

TGF-β1, IL-6, and TNF-α in Bronchoalveolar Lavage Fluid: Useful Markers for Lung Cancer?

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.

Utility of VEGF and sVEGFR-1 in bronchoalveolar lavage fluid for differential diagnosis of primary lung cancer.

Published data have shown that the levels of vascular endothelial growth factor (VEGF) and soluble VEGF receptor-1 (sVEGFR-1) in plasma and pleural effusion might be usefulness for lung cancer diagnosis. Here, we performed a prospective study to investigate the utility of VEGF and sVEGFR-1 in bronchoalveolar lavage fluid (BALF) for differential diagnosis of primary lung cancer. A total of 56 patients with solitary pulmonary massed by chest radiograph or CT screening were enrolled in this study. BALF and plasma samples were obtained from all patients and analyzed for VEGF and sVEGFR-1 using a commercially available sandwich ELISA kit. The results showed that the levels of VEGF in BALF were significantly higher in patients with a malignant pulmonary mass compared with patients with a benign mass (P < 0.001). However, no significant difference of sVEGFR-1 in BALF was found between malignant and non-malignant groups (P = 0.43). With a cut-off value of 214 pg/ml, VEGF showed a sensitivity and specificity of 81.8% and 84.2%, respectively, in predicting the malignant nature of a solitary pulmonary mass. Our study suggests that VEGF is significantly increased in BALF among patients with lung cancer than in benign diseases. Measurement of VEGF in BALF might be helpful for differential diagnosis of primary lung cancer.

Smoking-promoted oxidative DNA damage response is highly correlated to lung carcinogenesis

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.

Functional polymorphisms in the promoter region of MMP-2 and MMP-9 and susceptibility to obstructive sleep apnea.

Genetic susceptibility to obstructive sleep apnea (OSA) has been a research focus in the scientific community in the past few years. In this study, we recruited 375 subjects to investigate whether functional polymorphisms in the promoter region of matrix metalloproteinase (MMP)-2 (-1306C/T) and MMP-9 (-1562C/T) increased susceptibility to OSA. Our study showed no significant association between MMP-2 -1306C/T polymorphism and risk of OSA (T vs. C: OR = 1.01, 95% CI = 0.67–1.52; P = 0.97). Compared with the MMP-9 -1562C allele, the -1562T allele was associated with increased risk of OSA (T vs. C: OR = 1.56, 95% CI = 1.02–2.39; P = 0.04). However, neither MMP-2 -1306C/T nor MMP-9 -1562C/T polymorphism was found to be associated with severity of the disease. Our study suggested that the MMP-2 -1306C/T polymorphism was not associated with OSA susceptibility, whereas the MMP-9 -1562T allele was associated with increased risk of OSA.

Evaluation of VEGF-C and Tumor Markers in Bronchoalveolar Lavage Fluid for Lung Cancer Diagnosis

A total of 87 patients were enrolled and bronchoalveolar lavage fluid (BALF) samples were obtained from all subjects. A significant difference was found in BALF VEGF-C level between patients with squamous cell carcinoma and benign diseases (P = 0.043). In addition, the concentration of NSE in BALF form the malignant group was significantly higher compared with that of the benign groups (P = 0.018). However, no statistical difference was observed in BALF CEA (P = 0.375) or CYFRA21-1 (P = 0.838) between lung cancer patients and nonmalignant controls. With a cut-off value of 2.06 ng/ml, NSE had a sensitivity of 72.9%, a specificity of 69.2%, respectively, in predicting the malignant nature of pulmonary mass. Our study observed that the level of VEGF-C was increased in BALF of patients with squamous cell carcinoma. Moreover, we found that NSE was significantly higher in BALF of lung cancer patients than in benign diseases.

Vascular Endothelial Growth Factor Genotypes and Haplotypes Contribute to the Susceptibility of Obstructive Sleep Apnea Syndrome

Background To investigate whether VEGF polymorphisms (-460T/C, +405G/C, and +936C/T)/haplotypes influence the susceptibility of obstructive sleep apnea (OSA). Method A prospective case-control study was conducted to evaluate the genetic effects of VEGF polymorphisms on the development of OSA. 150 patients and 225 healthy controls were recruited for this study and their genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The odds ratios (OR) and 95% confidence intervals (CI) were calculated by logistic regression analysis. Result Our study showed that the -460C allele (C vs. T: OR = 1.95, 95% CI = 1.38–2.76) and +936T allele (T vs. C: OR = 1.48, 95% CI = 1.02–2.15) were associated with an increased OSA risk, whereas +405C allele was associated with a decreased susceptibility to OSA (C vs. G: OR = 0.61, 95% CI = 0.45–0.83). Compared with the most common haplotype CCT, CGC (OR = 2.22, 95% CI = 1.19–4.13) and TGC (OR = 3.83, 95% CI = 1.56–9.40) were associated with a significantly increased risk of OSA. Conclusion These observations implied that VEGF gene polymorphisms might be associated with the susceptibility to OSA. These results need to be validated by other independent studies, especially in diverse ethnic populations.

Diagnostic value of epidermal growth factor, cancer antigen 125, and cancer antigen 15-3 in bronchoalveolar lavage fluid of lung cancer

AIM In the present study, we assessed the diagnostic value of epidermal growth factor (egf) and cancer antigens 125 (ca125) and 15-3 (ca15-3) in bronchoalveolar lavage fluid (balf) of lung cancer from 79 enrolled patients with suspected lung cancer. METHODS All patients underwent fibrescopic examination, during which balf samples were collected. Levels of egf, ca125, and ca15-3 were determined in balf using commercially available test kits. RESULTS The results showed that levels of egf in balf were significantly higher in patients with lung cancer than in patients with benign diseases (p < 0.01); no significant differences for ca125 (p = 0.67) or ca15-3 (p = 0.43) in balf were observed between the lung cancer patients and the non-cancer control subjects. With a cut-off value of 27.22 pg/mL, egf showed a sensitivity of 63.6% and a specificity of 65.7% in predicting the malignant nature of pulmonary disease. CONCLUSIONS The study findings suggest that levels of egf are significantly increased in balf from patients with lung cancer than in balf from patients with benign disease. Detection of the level of egf in balf is proposed as a noninvasive test to identify patients at high risk for lung cancer.

Galactomannan in Bronchoalveolar Lavage Fluid for Diagnosis of Invasive Pulmonary Aspergillosis with Nonneutropenic Patients

Background We evaluated the utility of galactomannan (GM) in bronchoalveolar lavage fluid (BALF) for the diagnosis of invasive pulmonary aspergillosis (IPA) in nonneutropenic patients. Methods A total of 183 patients were included in the final analysis. Bronchoscopies and the detection of GM in BALF were all performed on them. Results Ten cases of IPA were diagnosed. ROC data demonstrated that, for diagnosing IPA, an optimal cutoff value for GM in BALF of 0.76 yielded a sensitivity of 100.0% and a specificity of 76.2%. Symptoms and radiological findings had no significant difference between proven or probable IPA group and non-IPA group. In our case-control analysis, although nine patients with false-positive results received treatment with Piperacillin/tazobactam, there was no significant difference between case and control group. Conclusions BALF GM detection is a valuable adjunctive diagnostic tool. Our retrospective study suggests that the optimal value of GM detection in BALF is 0.76 in nonneutropenic patients.

An unusual right hilar ‘mass’ with enlarged mediastinal lymph nodes

Introduction The imaging of lung cancer and pulmonary tuberculosis is extremely complex; an atypical radiological presentation can lead to diagnostic confusion when trying to distinguish between these two diseases. This article reports the case of a 46-year-old woman who presented with a dry cough. Chest computed tomography scan showed a right hilar mass with adjacent bronchial stenosis and multiple enlarged mediastinal lymph nodes that was initially diagnosed as squamous cell carcinoma of the lung. Multiple bronchoscopy biopsies showed some atypical epithelial cells and granulomas without necrosis, leading to the consideration of pulmonary tuberculosis. Chest imaging significantly improved after 7 months of anti-tuberculosis treatment. To the authors’ knowledge, this is the first reported case of lung consolidation caused by tuberculosis mimicking squamous cell carcinoma of the lung.