| Part I Molecular events during early human lung tumorigenesisIntroductionLung cancer results from the accumulation of various genetic alterations. It is of both clinical and scientific significance to study the molecular events during human lung tumorigenesis, especially in the early stage of lung cancer.Materials and MethodsIn this part of study,99 samples of airway epithelium from patients with peripheral pulmonary lesions (PPLs) and 41 tissue samples from patients with different stages of lung squamous carcinoma including precancerous lesions were collected from the Department of Endoscopy. Then mRNA of these samples was isolated and mRNA microarray was examined with Agilent SurePrint G3 Human GE v2 8x60K Microarray.ResultsFor the expression profiles of airway epithelium samples, the results were as follows: The gene expression of airway epithelium was affected by smoking. The majority biological processes involved in the decreased genes in airway epithelium of malignant PPLs were type I interferon signaling pathway, defense response, immune response, response to cytokine, response to stress and regulation of immune system process. The gene expression profiles of female nonsmokers’airway epithelium were influenced by the distal benign and malignant PPLs and the clinical stages. The down-regulating pathway in the airway epithelium of malignant PPLs from nonsmokers was related with immune, cell cycle, lipids metabolism, rRNA transcription, tRNA aminoacylation, while the up-regulating pathway was related with ribosome. A gradual up-regulation in interferon alpha/beta signaling during human fetal lung development was revealed, and the signaling was progressively down-regulated during human lung tumorigenesis. Moreover, the genes involved in this signaling might play a role in distinguishing certain clinical phenotypes. As for the tissue samples of different stages of human lung squamous carcinoma including precancerous lesions, the altered gene expression from severe dysplasia to stage I lung squamous carcinoma was found with the most notable significance during the lung tumorigenesis, and the molecular mechanism of this process was mainly related with extracellular matrix.ConclusionsTherefore, the gene expression profiles of airway epithelium might contribute to distinguishing benign from malignant PPLs, and could reveal the severity of malignant PPLs to a certain extent. And from its earliest stages, lung tumorigenesis was associated with decreased interferon alpha/beta signaling, and this association might provide insights for the selection of high-risk lung cancer patients. On the other hand, as for the tissue samples of lung squamous carcinoma, there were remarkable changes on genes related with extracellular matrix from severe dysplasia processed to stage I lung squamous carcinoma, and these molecular alterations might be the relative early events during lung tumorigenesis. significance during the lung tumorigenesis, and the molecular mechanism of this process was mainly related with extracellular matrix.ConclusionsTherefore, the gene expression profiles of airway epithelium might contribute to distinguishing benign from malignant PPLs, and could reveal the severity of malignant PPLs to a certain extent. And from its earliest stages, lung tumorigenesis was associated with decreased interferon alpha/beta signaling, and this association might provide insights for the selection of high-risk lung cancer patients. On the other hand, as for the tissue samples of lung squamous carcinoma, there were remarkable changes on genes related with extracellular matrix from severe dysplasia processed to stage I lung squamous carcinoma, and these molecular alterations might be the relative early events during lung tumorigenesis.Part Ⅱ Improve on the bronchoscopic brushing with a manual mapping method:a 3-year experience on 1143 casesIntroductionConventional bronchoscopy with brushing alone for diagnosing peripheral pulmonary lesions (PPLs) is of low sensitivity. A manual mapping method was introduced and evaluated in this study, which could be routinely applied with bronchoscopic brushing to improve the sensitivity for malignant PPLs.Materials and MethodsThis mapping method involves the bronchoscopist drawing the route with a series of bronchial opening sketches and marking the leading bronchus at every bifurcation point based on thin-section computed tomography. This map is then used to guide bronchoscope insertion for brushing. A cross-sectional study on the evaluation of this method for the diagnosis of malignant PPLs was conducted on patients from July 2010 to June 2013.ResultsThe sensitivity for malignant PPLs of conventional brushing, conventional brushing with mapping on a portion of patients and conventional brushing with mapping method increased from 17.0% to 25.8% to 31.5%(P<0.001), respectively. For lesion sizes over 3 cm, the rate of these three groups increased respectively from 25.1% to 38.6% to 50.9% (P<0.001). The sensitivity of this mapping method for malignant PPLs was statistically associated with lesion size, lesion character, relationship between the lesion and the leading bronchus, linear distance between the targeted bronchus and the opening of the lobe bronchus and the accessibility (P<0.001, P=0.039, P<0.001, P=0.031 and P=0.020, respectively).ConclusionsThis manual mapping method greatly increased the bronchoscopic brushing sensitivity for malignant PPLs compared to conventional brushing method. During routine clinical work, it is economical and convenient for guiding bronchoscope insertion in some extent. |
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