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Supplementary Tables 1-5 from Genome-Wide Gene Expression Changes in the Normal-Appearing Airway during the Evolution of Smoking-Associated Lung Adenocarcinoma

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posted on 2023-04-03, 22:01 authored by Jacob Kantrowitz, Ansam Sinjab, Li Xu, Tina L. McDowell, Smruthy Sivakumar, Wenhua Lang, Sayuri Nunomura-Nakamura, Junya Fukuoka, Georges Nemer, Nadine Darwiche, Hassan Chami, Arafat Tfayli, Ignacio I. Wistuba, Paul Scheet, Junya Fujimoto, Avrum E. Spira, Humam Kadara

Supplementary Tables Table S1. Early efffcts of NNK exposure on the mouse airway transcriptome. Table S2. Evolutionarily conserved decreased gene expression in the airway following NNK exposure. Table S3. Genes differentially regulated in the mouse airway at the indicated timepoints post NNK exposure. Table S4. Mouse genes downregulated as early as T2 vs T0 and enriched in airways of human smokers with lung cancer relative to cancer-free smokers. Table S5. Pathways analysis of Mouse genes enriched in airways of human smokers with lung cancer and modulated during in vivo lung oncogenesis

Funding

American Lung Association

American University of Beirut Collaborative Research Stimulus award

NCI

History

ARTICLE ABSTRACT

Smoking perpetuates in cytologically normal airways a molecular “field of injury” that is pertinent to lung cancer and early detection. The evolution of airway field changes prior to lung oncogenesis is poorly understood largely due to the long latency of lung cancer in smokers. Here, we studied airway expression changes prior to lung cancer onset in mice with knockout of the Gprc5a gene (Gprc5a−/−) and tobacco carcinogen (NNK) exposure and that develop the most common type of lung cancer, lung adenocarcinoma, within 6 months following exposure. Airway epithelial brushings were collected from Gprc5a−/− mice before exposure and at multiple times post-NNK until time of lung adenocarcinoma development and then analyzed by RNA sequencing. Temporal airway profiles were identified by linear models and analyzed by comparative genomics in normal airways of human smokers with and without lung cancer. We identified significantly altered profiles (n = 926) in the NNK-exposed mouse normal airways relative to baseline epithelia, a subset of which were concordantly modulated with smoking status in the human airway. Among airway profiles that were significantly modulated following NNK, we found that expression changes (n = 22) occurring as early as 2 months following exposure were significantly associated with lung cancer status when examined in airways of human smokers. Furthermore, a subset of a recently reported human bronchial gene classifier (Percepta; n = 56) was enriched in the temporal mouse airway profiles. We underscore evolutionarily conserved profiles in the normal-appearing airway that develop prior to lung oncogenesis and that comprise viable markers for early lung cancer detection in suspect smokers. Cancer Prev Res; 11(4); 237–48. ©2018 AACR.