Project description:Chronic obstructive pulmonary disease (COPD) is an independent risk factor for lung cancer, suggesting that COPD stroma favors cancer initiation. Therefore, we used proteomics and polysome-profiling to identify gene expression programs that distinguish stroma of patients harboring lung cancer from those that do not, with varied COPD severities. This profiling unveiled distinct COPD-dependent cancer-associated gene expression programs predominantly manifesting as alterations in mRNA translation. Mechanistically, such programs are downstream of the mammalian target of rapamycin pathway in mild COPD and pathological extracellular matrix in more severe COPD; and both programs parallel activation of distinct pro-cancer fibroblast-derived secretomes. Therefore, depending upon COPD severity, the lung stroma can exist in two states favoring cancer initiation, which likely result in distinct disease entities.
Project description:Interventions: Group 1: Quantitative Expression Analysis of the proteom and gene Expression of Primary Tumor, normal tissue, and metastases
Primary outcome(s): Disease associated Proteins and Genes
Study Design: Allocation: ; Masking: ; Control: ; Assignment: ; Study design purpose: basic science
