Distinct Cancer-Promoting Stromal Gene Expression Depending on Lung Function

Rationale: Chronic obstructive pulmonary disease (COPD) is an independent risk factor for lungcancer, but the underlying molecular mechanismsare unknown. We hypothesized that lungstromal cells activate pathological gene expression programssupporting oncogenesis. Objective: To identify molecular mechanismsoperating in the lungstroma that support development of lungcancer. Methods: Study subjects included patients with- or without- lungcancer across a spectrum of lungfunction. We conducted multi- omicsanalysis of non-malignant lungtissue to quantify the transcriptome, translatomeand proteome. Measurements and Main Results: Cancer-associated gene expression changes predominantly manifested as alterations in the efficiency of mRNA translation modulating protein levels in the absence of corresponding changes in mRNA levels. The molecular mechanismsdriving these cancer-associated translation programs differed basedon lungfunction. In subjects with normal to mildly impaired lung-function, the mamma...