Identification and Characterization of Metastasis-Related Protein Marker for Non-Small Cell Lung Cancer by Quantitative Tissue and Pleural Effusion Proteomes

Lung cancer is the most common type of cancer worldwide accounting for 12.4% of all newly diagnosed cases and represents the leading cause of cancer-related deaths in the world. Non-small cell lung cancer (NSCLC) is the most common lung cancer type, comprising ~80% of all lung cancers. Despite major advances in cancer therapy over the past two decades, the prognosis of patients with NSCLC has improved only minimally. The overall 5-year survival for NSCLC remains at only 15%; however, if the cancer is detected at stage IA, the 5-year survival often exceeds 80%. It means that the stage of lung cancer is highly related to prognosis and the degree of cancer spread to lymph nodes is a critical component in the staging process. In this proposal, to gain the metastasis-related biomarkers, we will first generate the differential protein profiles from two types of clinical specimens by quantitative proteomic technologies. One is the lung cancer tissues with different pathological stages (early vs advanced stage) and the other is the pleural effusion (PE) from patients with NSCLC, pneumonia or tuberculosis. Next, we will integrate the differential tissue, pleural effusion proteomes and cancer cell secretome to generate a potential biomarker dataset for lung cancer metastasis. The potential metastasis-related protein markers will be validated by using clinical specimens. To address the molecular mechanisms of these metastasis-related biomarkers, we will combine molecular biology, cell biology, quantitative proteomics and xenograft mice models to characterize the regulations of these proteins involved in lung cancer progression. This proposal would be the first study to search metastasis-related biomarker for NSCLC by integration of quantitative tissue and PE proteomes. The goal of this proposal is to discover and address the mechanism of metastasis-related proteins for prognosis and therapeutic development of NSCLC. Our specific aims are: 1. Generate a metastasis-related biomarker dataset for NSCLC. a. Generate a malignancy-related PE proteome dataset by identification of differential protein profiles from three types of pleural effusions (NSCLC, pneumonia and tuberculosis). b. Generate a stage-related tissue proteome dataset by identification of differential protein profiles from paired adenocarcinoma cancer tissues with different stages (stage I, II and advanced stage). c. Combine PE proteome, tissue proteome and cancer cell secretome to search metastasis-related biomarker candidates. 2. Develop biomarkers for prognosis of NSCLC. a. Validate the clinical significance of metastasis-related biomarkers by using large scale of clinical specimens. 3. Determine the molecular mechanism of the promising biomarker in tumor metastasis. a. Characterize the biological function of biomarker in cell and xenograft mouse model. b. Define the relationship between well-known signaling molecules or discover the novel interaction network of promising biomarker by quantitative proteomic strategy.

Project ID:PC10008-0509
External Project ID:NSC100-2320-B182-025