Portal de Periódicos da CAPES

Lung tissue shows divergent gene expression between chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis

2022; BioMed Central; Volume: 23; Issue: 1 Linguagem: Inglês

10.1186/s12931-022-02013-w

1465-993X

Auyon Ghosh, Brian D. Hobbs, Jeong H. Yun, Aabida Saferali, Matthew Moll, Zhonghui Xu, Robert Chase, Jarrett D. Morrow, John Ziniti, Frank C. Sciurba, Lucas Barwick, Andrew H. Limper, Kevin R. Flaherty, Gerard J. Criner, Kevin K. Brown, Robert A. Wise, Fernando J. Martínez, Daniel McGoldrick, Michael H. Cho, Dawn L. DeMeo, Edwin K. Silverman, Peter J. Castaldi, James D. Crapo, Edwin K. Silverman, Barry J. Make, Elizabeth A. Regan, Terri H. Beaty, Ferdouse Begum, Peter J. Castaldi, Michael H. Cho, Dawn L. DeMeo, Adel R. Boueiz, Marilyn G. Foreman, Eitan Halper-Stromberg, Lystra P. Hayden, Craig P. Hersh, Jacqueline B. Hetmanski, Brian D. Hobbs, John E. Hokanson, Nan M. Laird, Christoph Lange, Sharon M. Lutz, Merry‐Lynn McDonald, Margaret M. Parker, Dmitry Prokopenko, Dandi Qiao, Phuwanat Sakornsakolpat, Emily S. Wan, Sungho Won, Juan Pablo Centeno, Jean‐Paul Charbonnier, Harvey O. Coxson, Craig J. Galbán, MeiLan K. Han, Eric A. Hoffman, Stephen M. Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, Pietro Nardelli, John D. Newell, Aleena Notary, Andrea Oh, James C. Ross, Raúl San Jośe Estépar, Joyce Schroeder, Jered Sieren, Berend C. Stoel, Juerg Tschirren, Edwin J.R. van Beek, Bram van Ginneken, Eva M. van Rikxoort, Gonzalo Vegas‐Sánchez‐Ferrero, Lucas Veitel, George R. Washko, Carla G. Wilson, Robert L. Jensen, Douglas Curran‐Everett, Jim Crooks, Katherine Pratte, Matthew Strand, Gregory L. Kinney, Kendra A. Young, Surya P. Bhatt, Jessica Bon, Alejandro A. Díaz, Susan Murray, Xavier Soler, Russell P. Bowler, Katerina Kechris, Farnoush Banaei‐Kashani, Jeffrey L. Curtis, Perry G. Pernicano, Nicola A. Hanania, Mustafa Atik, Aladin M. Boriek, Kalpatha Guntupalli, Elizabeth Guy, Amit Parulekar, R. Graham Barr, John Austin, Belinda D’Souza, Byron Thomashow, Neil MacIntyre, H. Page McAdams, Lacey Washington, Eric L. Flenaugh, Silanth Terpenning, Charlene McEvoy, Joseph Tashjian, Robert A. Wise, Robert Brown, Nadia N. Hansel, Karen M. Horton, Allison Lambert, Nirupama Putcha, Richard Casaburi, Alessandra Adami, Matthew J. Budoff, H. Keith Fischer, János Pórszász, Harry B. Rossiter, William W. Stringer, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Ken M. Kunisaki, Richard Rosiello, David Pace, Gerard J. Criner, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert E. D’Alonzo, Parag Desai, Michael E. Jacobs, Steven G. Kelsen, V. Kim, A. James Mamary, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M. Steiner, Alex Swift, Irene Swift, Maria Elena Vega‐Sanchez, Mark Dransfield, William C. Bailey, Anand Iyer, Hrudaya Nath, J. Michael Wells, Douglas Conrad, Andrew Yen, Alejandro P. Comellas, Karin F. Hoth, Brad Thompson, Wassim W. Labaki, Dharshan Vummidi, Joanne Billings, Abbie Begnaud, Tadashi Allen, Frank C. Sciurba, Divay Chandra, Carl R. Fuhrman, Joel L. Weissfeld, Antonio Anzueto, Sylvia Adams, Diego Maselli-Caceres, Mario E. Ruiz, Harjinder Sing, Craig P. Hersh,

Occupational and environmental lung diseases

Chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are characterized by shared exposures and clinical features, but distinct genetic and pathologic features exist. These features have not been well-studied using large-scale gene expression datasets. We hypothesized that there are divergent gene, pathway, and cellular signatures between COPD and IPF.We performed RNA-sequencing on lung tissues from individuals with IPF (n = 231) and COPD (n = 377) compared to control (n = 267), defined as individuals with normal spirometry. We grouped the overlapping differential expression gene sets based on direction of expression and examined the resultant sets for genes of interest, pathway enrichment, and cell composition. Using gene set variation analysis, we validated the overlap group gene sets in independent COPD and IPF data sets.We found 5010 genes differentially expressed between COPD and control, and 11,454 genes differentially expressed between IPF and control (1% false discovery rate). 3846 genes overlapped between IPF and COPD. Several pathways were enriched for genes upregulated in COPD and downregulated in IPF; however, no pathways were enriched for genes downregulated in COPD and upregulated in IPF. There were many myeloid cell genes with increased expression in COPD but decreased in IPF. We found that the genes upregulated in COPD but downregulated in IPF were associated with lower lung function in the independent validation cohorts.We identified a divergent gene expression signature between COPD and IPF, with increased expression in COPD and decreased in IPF. This signature is associated with worse lung function in both COPD and IPF.