Myocyte enhancer factor 2D provides a cross-talk between chronic inflammation and lung cancer.

BACKGROUND: Lung cancer is the leading cause of cancer-related morbidity and mortality worldwide. Patients with chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD), are exposed to a higher risk of developing lung cancer. Chronic inflammation may play an important role in the lung carcinogenesis among those patients. The present study aimed at identifying candidate biomarker predicting lung cancer risk among patients with chronic respiratory diseases. METHODS: We applied clinical bioinformatics tools to analyze different gene profile datasets with a special focus on screening the potential biomarker during chronic inflammation-lung cancer transition. Then we adopted an in vitro model based on LPS-challenged A549 cells to validate the biomarker through RNA-sequencing, quantitative real time polymerase chain reaction, and western blot analysis. RESULTS: Bioinformatics analyses of the 16 enrolled GSE datasets from Gene Expression Omnibus online database showed myocyte enhancer factor 2D (MEF2D) level significantly increased in COPD patients coexisting non-small-cell lung carcinoma (NSCLC). Inflammation challenge increased MEF2D expression in NSCLC cell line A549, associated with the severity of inflammation. Extracellular signal-regulated protein kinase inhibition could reverse the up-regulation of MEF2D in inflammation-activated A549. MEF2D played a critical role in NSCLC cell bio-behaviors, including proliferation, differentiation, and movement. CONCLUSIONS: Inflammatory conditions led to increased MEF2D expression, which might further contribute to the development of lung cancer through influencing cancer microenvironment and cell bio-behaviors. MEF2D might be a potential biomarker during chronic inflammation-lung cancer transition, predicting the risk of lung cancer among patients with chronic respiratory diseases.

Impaired self-healing capacity in airway epithelia lacking aquaporin-3.

In this study, we utilized AQP3-knockout mice as the in vivo model and AQP3-knockdown human bronchial epithelial cells (HBECs) as the in vitro model. Airway injury was experimentally induced by intra-tracheal injection of naphthalene. HE staining, transmission and scanning electron microscope were performed to evaluate self-healing capacity in vivo. Transwell and wound-healing assays were performed to evaluate epithelial cell migration in vitro. We found that both the airway epithelial cells of AQP3-knockout mice and AQP3-knockdown HBECs exhibited an obviously impaired self-healing capacity with defective epithelial cell migration through AQP3-facilitated glycerol transport. In addition, glycerol supplementation could largely correct defective injury healing and epithelial cell migration. For the first time, we found evidence for distinct defects in AQP3-deficient airway epithelial cell migration. Mechanistic analysis showed AQP3-facillitated glycerol transport plays a role in airway epithelial self-healing after injury.

Role of a serum-based biomarker panel in the early diagnosis of lung cancer for a cohort of high-risk patients.

BACKGROUND: This study applied a combined cancer biomarker panel to clinically identify small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) in a high-risk population. METHODS: The serum levels of 4 biomarkers (progastrin-releasing peptide [ProGRP], carcinoembryonic antigen [CEA], squamous cell carcinoma antigen [SCC], and cytokeratin 19 fragment [CYFRA21-1]) were determined in 153 patients with a high risk of lung cancer (12 with a new diagnosis of SCLC, 52 with NSCLC, and 89 without lung cancer). Information about diagnosis delays was collected through interviews of all participants. RESULTS: Significantly higher serum levels of ProGRP (P < .0001) were found among the SCLC patients versus the rest of the population. A receiver operating characteristic curve analysis established the cutoff values of ProGRP, CEA, SCC, and CYFRA21-1 as 300 pg/mL, 7.3 ng/mL, 3 ng/mL, and 6.5 ng/mL, respectively. The sensitivity and specificity of ProGRP in diagnosing SCLC were 75% and 100%, respectively. Among the 14 lung cancer patients with a false-negative computed tomography (CT) result, the diagnostic panel detected 8 additional cancers. CONCLUSIONS: This panel increased the diagnostic specificity for high-risk subjects (those with renal failure being excluded), and auxiliary to a CT scan, it increased the sensitivity for patients with lung cancer. These results might be applied to shorten the diagnosis delay at health care institutions in China.

Prevalence of undiagnosed and undertreated chronic obstructive pulmonary disease in lung cancer population.

BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a risk factor and important coexisting disease for lung cancer; however, the current status of management of COPD in lung cancer patients is not fully described. This study addressed this issue in a general teaching hospital in China. METHODS: Medical records of hospitalized lung cancer patients in Zhongshan Hospital, Fudan University, between January 2006 and December 2010 were reviewed. The definition of COPD was according to the spirometric criteria of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) document. The diagnostic rate (COPD recorded as a discharge diagnosis/spirometry-defined percentage) and conformity to GOLD treatment guidelines were investigated. The factors influencing diagnosis were analysed. RESULTS: During the study period, the prevalence of spirometry-defined COPD in hospitalized lung cancer patients was 21.6% (705/3263). The overall diagnostic rate of COPD was 7.1%, and the treatment conformity for stable and acute exacerbation of COPD was 27.1% and 46.8%, respectively. Respiratory physicians had a higher diagnostic rate than non-respiratory doctors (34.8% vs 2.9%, P < 0.001) and a better treatment conformity for acute exacerbation of COPD (63.6% vs 37.5%, P = 0.048). Patients with COPD as a discharge diagnosis had more chance to receive guideline-consistent treatment. The diagnostic rate of COPD was higher among patients with a history of smoking, respiratory diseases or symptoms. CONCLUSIONS: COPD is substantially underdiagnosed and undertreated in a hospitalized lung cancer population. History of smoking, respiratory diseases and symptoms promotes diagnosis. Education of COPD knowledge among patients and doctors is urgently required in this special population.