Investigating genetic drivers of dermatomyositis pathogenesis using meta-analysis
Aims: Dermatomyositis (DM) is a progressive, idiopathic inflammatory myopathy with poorly understood pathogenesis. A hallmark of DM is an increased risk for developing breast, ovarian, and lung cancer. Since autoantibodies against anti-TIF-1-γ, a member of the tripartite motif (TRIM) proteins, has a...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-09-01
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| Series: | Heliyon |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844020317096 |
| _version_ | 1819003673780420608 |
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| author | Jihad Aljabban Saad Syed Sharjeel Syed Michael Rohr Noah Weisleder Kevin E. McElhanon Laith Hasan Laraib Safeer Kalyn Hoffman Nabeal Aljabban Mohamed Mukhtar Nikhil Adapa Zahir Allarakhia Maryam Panahiazar Isaac Neuhaus Susan Kim Dexter Hadley Wael Jarjour |
| author_facet | Jihad Aljabban Saad Syed Sharjeel Syed Michael Rohr Noah Weisleder Kevin E. McElhanon Laith Hasan Laraib Safeer Kalyn Hoffman Nabeal Aljabban Mohamed Mukhtar Nikhil Adapa Zahir Allarakhia Maryam Panahiazar Isaac Neuhaus Susan Kim Dexter Hadley Wael Jarjour |
| author_sort | Jihad Aljabban |
| collection | DOAJ |
| description | Aims: Dermatomyositis (DM) is a progressive, idiopathic inflammatory myopathy with poorly understood pathogenesis. A hallmark of DM is an increased risk for developing breast, ovarian, and lung cancer. Since autoantibodies against anti-TIF-1-γ, a member of the tripartite motif (TRIM) proteins, has a strong association with malignancy, we examined expression of the TRIM gene family to identify pathways that may be contributing to DM pathogenesis. Materials and methods: We employed the Search Tag Analyze Resource for GEO platform to search the NCBI Gene Expression Omnibus to elucidate TRIM family gene expression as well as oncogenic drivers in DM pathology. We conducted meta-analysis of the data from human skin (60 DM vs 34 healthy) and muscle (71 DM vs 22 healthy). Key findings: We identified genes involved in innate immunity, antigen presentation, metabolism, and other cellular processes as facilitators of DM disease activity and confirmed previous observations regarding the presence of a robust interferon signature. Moreover, analysis of DM muscle samples revealed upregulation of TRIM14, TRIM22, TRIM25, TRIM27, and TRIM38. Likewise, analysis of DM skin samples showed upregulation of TRIM5, TRIM6, TRIM 14, TRIM21, TRIM34, and TRIM38 and downregulation of TRIM73. Additionally, we noted upregulation of oncogenes IGLC1, IFI44, POSTN, MYC, NPM1, and IDO1 and related this change to interferon signaling. While the clinical data associated with genetic data that was analyzed did not contain clinical data regarding malignancy in these cohorts, the observed genetic changes may be associated with homeostatic and signaling changes that relate to the increased risk in malignancy in DM. Significance: Our results implicate previously unknown genes as potential drivers of DM pathology and suggest certain TRIM family members may have disease-specific roles with potential diagnostic and therapeutic implications. |
| first_indexed | 2024-12-20T23:24:45Z |
| format | Article |
| id | doaj.art-69b214ceceef4e5489ce1d16e32be58e |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-12-20T23:24:45Z |
| publishDate | 2020-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-69b214ceceef4e5489ce1d16e32be58e2022-12-21T19:23:25ZengElsevierHeliyon2405-84402020-09-0169e04866Investigating genetic drivers of dermatomyositis pathogenesis using meta-analysisJihad Aljabban0Saad Syed1Sharjeel Syed2Michael Rohr3Noah Weisleder4Kevin E. McElhanon5Laith Hasan6Laraib Safeer7Kalyn Hoffman8Nabeal Aljabban9Mohamed Mukhtar10Nikhil Adapa11Zahir Allarakhia12Maryam Panahiazar13Isaac Neuhaus14Susan Kim15Dexter Hadley16Wael Jarjour17University of Wisconsin Hospital and Clinics, Madison, WI, USAStanford University School of Medicine, Palo Alto, CA, USAUniversity of Chicago Medical Center, Chicago, IL, USAUniversity of Central Florida College of Medicine, Orlando, FL, USAThe Ohio State University College of Medicine, Columbus, OH, USAThe Ohio State University College of Medicine, Columbus, OH, USATulane School of Medicine, New Orleans, LA, USABaylor College of Medicine, Houston, TX, USAThe Ohio State University College of Medicine, Columbus, OH, USAPennsylvannia State College of Medicine, Hershey, PA, USAMichigan State University College of Human Medicine, Lansing, MI, USASUNY Upstate Medical Center, Syracuse, NY, USAThe Ohio State University College of Medicine, Columbus, OH, USAUniversity of California San Francisco, San Francisco, CA, USAUniversity of California San Francisco, San Francisco, CA, USAUniversity of California San Francisco, San Francisco, CA, USAUniversity of Central Florida College of Medicine, Orlando, FL, USAThe Ohio State University College of Medicine, Columbus, OH, USA; Corresponding author.Aims: Dermatomyositis (DM) is a progressive, idiopathic inflammatory myopathy with poorly understood pathogenesis. A hallmark of DM is an increased risk for developing breast, ovarian, and lung cancer. Since autoantibodies against anti-TIF-1-γ, a member of the tripartite motif (TRIM) proteins, has a strong association with malignancy, we examined expression of the TRIM gene family to identify pathways that may be contributing to DM pathogenesis. Materials and methods: We employed the Search Tag Analyze Resource for GEO platform to search the NCBI Gene Expression Omnibus to elucidate TRIM family gene expression as well as oncogenic drivers in DM pathology. We conducted meta-analysis of the data from human skin (60 DM vs 34 healthy) and muscle (71 DM vs 22 healthy). Key findings: We identified genes involved in innate immunity, antigen presentation, metabolism, and other cellular processes as facilitators of DM disease activity and confirmed previous observations regarding the presence of a robust interferon signature. Moreover, analysis of DM muscle samples revealed upregulation of TRIM14, TRIM22, TRIM25, TRIM27, and TRIM38. Likewise, analysis of DM skin samples showed upregulation of TRIM5, TRIM6, TRIM 14, TRIM21, TRIM34, and TRIM38 and downregulation of TRIM73. Additionally, we noted upregulation of oncogenes IGLC1, IFI44, POSTN, MYC, NPM1, and IDO1 and related this change to interferon signaling. While the clinical data associated with genetic data that was analyzed did not contain clinical data regarding malignancy in these cohorts, the observed genetic changes may be associated with homeostatic and signaling changes that relate to the increased risk in malignancy in DM. Significance: Our results implicate previously unknown genes as potential drivers of DM pathology and suggest certain TRIM family members may have disease-specific roles with potential diagnostic and therapeutic implications.http://www.sciencedirect.com/science/article/pii/S2405844020317096BioinformaticsGeneticsImmunologyMolecular biologyPathologyDermatomyositis |
| spellingShingle | Jihad Aljabban Saad Syed Sharjeel Syed Michael Rohr Noah Weisleder Kevin E. McElhanon Laith Hasan Laraib Safeer Kalyn Hoffman Nabeal Aljabban Mohamed Mukhtar Nikhil Adapa Zahir Allarakhia Maryam Panahiazar Isaac Neuhaus Susan Kim Dexter Hadley Wael Jarjour Investigating genetic drivers of dermatomyositis pathogenesis using meta-analysis Heliyon Bioinformatics Genetics Immunology Molecular biology Pathology Dermatomyositis |
| title | Investigating genetic drivers of dermatomyositis pathogenesis using meta-analysis |
| title_full | Investigating genetic drivers of dermatomyositis pathogenesis using meta-analysis |
| title_fullStr | Investigating genetic drivers of dermatomyositis pathogenesis using meta-analysis |
| title_full_unstemmed | Investigating genetic drivers of dermatomyositis pathogenesis using meta-analysis |
| title_short | Investigating genetic drivers of dermatomyositis pathogenesis using meta-analysis |
| title_sort | investigating genetic drivers of dermatomyositis pathogenesis using meta analysis |
| topic | Bioinformatics Genetics Immunology Molecular biology Pathology Dermatomyositis |
| url | http://www.sciencedirect.com/science/article/pii/S2405844020317096 |
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