Project description:Previous work has shown that lung tumors and normal-appearing adjacent lung tissues share specific abnormalities that may be highly pertinent to the pathogenesis of lung cancer. However, the global and molecular adjacent airway field cancerization in non-small cell lung cancer (NSCLC) has not been characterized before. We sought to understand the transcriptomic architecture of the adjacent airway field canerization, in conjunction with tumors, to gain additional insights into the lung cancer biology and oncogenesis. We analyzed the transcriptome, using the Affymetrix Human Gene 1.0 ST platform, of matched NSCLC tumors, multiple normal airway epithelia with differential distance from the tumors as well as uninvolved normal lung tissues. We analyzed the airway field cancerization transcritpome to determine global differentially expressed cancerization profiles in adjacent airways as well as airway profiles that may be modulated by distance from tumors.
Project description:We recently characterized the adjacent airway field of cancerization in NSCLC by whole transcriptome expression analysis and demonstrated that lysosomal protein transmembrane 4 beta (LAPTM4B) was an elevated field cancerization marker in NSCLCs and in adjacent but not in distant normal-appearing airways. We also found that LAPTM4B was up-regulated in NSCLCs compared to normal lung and promoted anchorage-dependent growth of lung cancer cells. Previous reports suggested that LAPTM4B is activated following metabolic and genotixc stress. The precise role of LAPTM4B in lung cancer cell survival and NSCLC pathogenesis is still elusive.
Project description:Previous work has shown that lung tumors and normal-appearing adjacent lung tissues share specific abnormalities that may be highly pertinent to the pathogenesis of lung cancer. However, the global and molecular adjacent airway field cancerization in non-small cell lung cancer (NSCLC) has not been characterized before. We sought to understand the transcriptomic architecture of the adjacent airway field canerization, in conjunction with tumors, to gain additional insights into the lung cancer biology and oncogenesis.
Project description:Field of cancerization in the airway epithelium has been increasing examined to understand early pathogenesis of non-small cell lung cancer. This study uses microarray high-throughput technologies to characterize the molecular aberrations in the terminal airway and bronchoalveolar cells in the context of field cancerization in high-risk smokers and lung cancer patients.
Project description:Field of cancerization in the airway epithelium has been increasing examined to understand early pathogenesis of non-small cell lung cancer. This study uses microarray high-throughput technologies to characterize the molecular aberrations in the terminal airway and bronchoalveolar cells in the context of field cancerization in high-risk smokers and lung cancer patients.
Project description:We recently characterized the adjacent airway field of cancerization in NSCLC by whole transcriptome expression analysis and demonstrated that lysosomal protein transmembrane 4 beta (LAPTM4B) was an elevated field cancerization marker in NSCLCs and in adjacent but not in distant normal-appearing airways. We also found that LAPTM4B was up-regulated in NSCLCs compared to normal lung and promoted anchorage-dependent growth of lung cancer cells. Previous reports suggested that LAPTM4B is activated following metabolic and genotixc stress. The precise role of LAPTM4B in lung cancer cell survival and NSCLC pathogenesis is still elusive. In the present study we sought to examine how LAPTM4B expression levels impact downstream expression profiles and cell signaling in order to gain better insights into the function of this putative oncogene in lung cancer. Calu-6 lung cancer cells were transfected with SMARTpool (Dharmacon)control/scrambled siRNA or siRNA targeting LAPTM4B. Following transfection, cells were cultured in the presence or absence of 10% fetal bovine serum (FBS). Three independent transfections for each condition were performed representing three biological replicates per condition (total number of samples = 12). RNA interference-mediated knock-down of LAPTM4B in samples was confirmed by quantitative real-time PCR. Total RNA was profiled using the Human Gene 1.0 ST platform.
Project description:Field of cancerization in the airway epithelium has been increasing examined to understand early pathogenesis of non-small cell lung cancer. This study uses microarray high-throughput technologies to characterize the molecular aberrations in the terminal airway and bronchoalveolar cells in the context of field cancerization in high-risk smokers and lung cancer patients. We collected peripheral airway brushings from the contral-lateral lung of the tumor from cancer patients (n=17) and smoker controls (n=13); Total RNA were obtained from the peripheral airway epithelium.
Project description:Field of cancerization in the airway epithelium has been increasing examined to understand early pathogenesis of non-small cell lung cancer. This study uses microarray high-throughput technologies to characterize the molecular aberrations in the terminal airway and bronchoalveolar cells in the context of field cancerization in high-risk smokers and lung cancer patients. We collected peripheral airway brushings from the contral-lateral lung of the tumor from cancer patients (n=17) and smoker controls (n=13); Total RNA were obtained from the peripheral airway epithelium.