Characterization of monoclonal gammopathy of undetermined significance progression to multiple myeloma through meta-analysis of GEO data
The etiology of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) is still obscure as are the processes that enable the progression of MGUS to MM. Understanding the unique vs. shared transcriptomes can potentially elucidate why individuals develop one or the other....
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-07-01
|
| Series: | Heliyon |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023045061 |
| _version_ | 1797771541260271616 |
|---|---|
| author | Jihad Aljabban Sharjeel Syed Saad Syed Michael Rohr Mohamed Mukhtar Hisham Aljabban Francesca Cottini Mohammed Mohammed Tiffany Hughes Taylor Gonzalez Maryam Panahiazr Dexter Hadley Don Benson |
| author_facet | Jihad Aljabban Sharjeel Syed Saad Syed Michael Rohr Mohamed Mukhtar Hisham Aljabban Francesca Cottini Mohammed Mohammed Tiffany Hughes Taylor Gonzalez Maryam Panahiazr Dexter Hadley Don Benson |
| author_sort | Jihad Aljabban |
| collection | DOAJ |
| description | The etiology of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) is still obscure as are the processes that enable the progression of MGUS to MM. Understanding the unique vs. shared transcriptomes can potentially elucidate why individuals develop one or the other. Furthermore, highlighting key pathways and genes involved in the pathogenesis of MM or the development of MGUS to MM may allow the discovery of novel drug targets and therapies.We employed STARGEO platform to perform three separate meta-analysis to compare MGUS and MM transcriptomes. For these analyses we tagged (1) 101 MGUS patient plasma cells from bone marrow samples and 64 plasma cells from healthy controls (2) 383 MM patient CD138+ cells from bone marrow and the 101 MGUS samples in the first analysis as controls (3) 517 MM patient peripheral blood samples and 97 peripheral blood samples from healthy controls. We then utilized Ingenuity Pathway Analysis (IPA) to analyze the unique genomic signatures within and across these samples.Our study identified genes that may have unique roles in MGUS (GADD45RA and COMMD3), but also newly identified signaling pathways (EIF2, JAK/STAT, and MYC) and gene activity (NRG3, RBFOX2, and PARP15) in MGUS that have previously been shown to be involved in MM suggesting a spectrum of molecular overlap. On the other hand, genes such as DUSP4, RN14, LAMP5, differentially upregulated in MM, may be seen as tipping the scales from benignity to malignancy and could serve as drug targets or novel biomarkers for risk of progression. Furthermore, our analysis of MM identified newly associated gene/pathway activity such as inhibition of Wnt-signaling and defective B cell development. Finally, IPA analysis, suggests the multifactorial, oncogenic qualities of IFNγ signaling in MM may be a unifying pathway for these diverse mechanisms and prompts the need for further studies. |
| first_indexed | 2024-03-12T21:39:06Z |
| format | Article |
| id | doaj.art-0b306d964442417296de4dd2df11a8e2 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-12T21:39:06Z |
| publishDate | 2023-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-0b306d964442417296de4dd2df11a8e22023-07-27T05:56:23ZengElsevierHeliyon2405-84402023-07-0197e17298Characterization of monoclonal gammopathy of undetermined significance progression to multiple myeloma through meta-analysis of GEO dataJihad Aljabban0Sharjeel Syed1Saad Syed2Michael Rohr3Mohamed Mukhtar4Hisham Aljabban5Francesca Cottini6Mohammed Mohammed7Tiffany Hughes8Taylor Gonzalez9Maryam Panahiazr10Dexter Hadley11Don Benson12University of Wisconsin Hospital and Clinics, Department of Medicine, United States; Corresponding author.University of Chicago Medical Center, Department of Medicine, United StatesNorthwestern Memorial Hospital, Department of Medicine, United StatesUniversity of Central Florida College of Medicine, United StatesMichigan State University College of Human Medicine, United StatesRegis University, United StatesOhio State University Wexner Medical Center, United States; James Cancer Hospital Solove Research Institute, United StatesWindsor University School of Medicine, United StatesOhio State University Wexner Medical Center, United StatesOhio State University Wexner Medical Center, United StatesUniversity of California San Francisco, Department of Surgery, United StatesUniversity of Central Florida College of Medicine, United States; University of Central Florida, Chief of the Department of Artificial Intelligence, United StatesOhio State University Wexner Medical Center, United States; James Cancer Hospital Solove Research Institute, United StatesThe etiology of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) is still obscure as are the processes that enable the progression of MGUS to MM. Understanding the unique vs. shared transcriptomes can potentially elucidate why individuals develop one or the other. Furthermore, highlighting key pathways and genes involved in the pathogenesis of MM or the development of MGUS to MM may allow the discovery of novel drug targets and therapies.We employed STARGEO platform to perform three separate meta-analysis to compare MGUS and MM transcriptomes. For these analyses we tagged (1) 101 MGUS patient plasma cells from bone marrow samples and 64 plasma cells from healthy controls (2) 383 MM patient CD138+ cells from bone marrow and the 101 MGUS samples in the first analysis as controls (3) 517 MM patient peripheral blood samples and 97 peripheral blood samples from healthy controls. We then utilized Ingenuity Pathway Analysis (IPA) to analyze the unique genomic signatures within and across these samples.Our study identified genes that may have unique roles in MGUS (GADD45RA and COMMD3), but also newly identified signaling pathways (EIF2, JAK/STAT, and MYC) and gene activity (NRG3, RBFOX2, and PARP15) in MGUS that have previously been shown to be involved in MM suggesting a spectrum of molecular overlap. On the other hand, genes such as DUSP4, RN14, LAMP5, differentially upregulated in MM, may be seen as tipping the scales from benignity to malignancy and could serve as drug targets or novel biomarkers for risk of progression. Furthermore, our analysis of MM identified newly associated gene/pathway activity such as inhibition of Wnt-signaling and defective B cell development. Finally, IPA analysis, suggests the multifactorial, oncogenic qualities of IFNγ signaling in MM may be a unifying pathway for these diverse mechanisms and prompts the need for further studies.http://www.sciencedirect.com/science/article/pii/S2405844023045061Multiple myelomaMonoclonal gammopathyInterferon gammaBioinformaticsGene expression omnibus |
| spellingShingle | Jihad Aljabban Sharjeel Syed Saad Syed Michael Rohr Mohamed Mukhtar Hisham Aljabban Francesca Cottini Mohammed Mohammed Tiffany Hughes Taylor Gonzalez Maryam Panahiazr Dexter Hadley Don Benson Characterization of monoclonal gammopathy of undetermined significance progression to multiple myeloma through meta-analysis of GEO data Heliyon Multiple myeloma Monoclonal gammopathy Interferon gamma Bioinformatics Gene expression omnibus |
| title | Characterization of monoclonal gammopathy of undetermined significance progression to multiple myeloma through meta-analysis of GEO data |
| title_full | Characterization of monoclonal gammopathy of undetermined significance progression to multiple myeloma through meta-analysis of GEO data |
| title_fullStr | Characterization of monoclonal gammopathy of undetermined significance progression to multiple myeloma through meta-analysis of GEO data |
| title_full_unstemmed | Characterization of monoclonal gammopathy of undetermined significance progression to multiple myeloma through meta-analysis of GEO data |
| title_short | Characterization of monoclonal gammopathy of undetermined significance progression to multiple myeloma through meta-analysis of GEO data |
| title_sort | characterization of monoclonal gammopathy of undetermined significance progression to multiple myeloma through meta analysis of geo data |
| topic | Multiple myeloma Monoclonal gammopathy Interferon gamma Bioinformatics Gene expression omnibus |
| url | http://www.sciencedirect.com/science/article/pii/S2405844023045061 |
| work_keys_str_mv | AT jihadaljabban characterizationofmonoclonalgammopathyofundeterminedsignificanceprogressiontomultiplemyelomathroughmetaanalysisofgeodata AT sharjeelsyed characterizationofmonoclonalgammopathyofundeterminedsignificanceprogressiontomultiplemyelomathroughmetaanalysisofgeodata AT saadsyed characterizationofmonoclonalgammopathyofundeterminedsignificanceprogressiontomultiplemyelomathroughmetaanalysisofgeodata AT michaelrohr characterizationofmonoclonalgammopathyofundeterminedsignificanceprogressiontomultiplemyelomathroughmetaanalysisofgeodata AT mohamedmukhtar characterizationofmonoclonalgammopathyofundeterminedsignificanceprogressiontomultiplemyelomathroughmetaanalysisofgeodata AT hishamaljabban characterizationofmonoclonalgammopathyofundeterminedsignificanceprogressiontomultiplemyelomathroughmetaanalysisofgeodata AT francescacottini characterizationofmonoclonalgammopathyofundeterminedsignificanceprogressiontomultiplemyelomathroughmetaanalysisofgeodata AT mohammedmohammed characterizationofmonoclonalgammopathyofundeterminedsignificanceprogressiontomultiplemyelomathroughmetaanalysisofgeodata AT tiffanyhughes characterizationofmonoclonalgammopathyofundeterminedsignificanceprogressiontomultiplemyelomathroughmetaanalysisofgeodata AT taylorgonzalez characterizationofmonoclonalgammopathyofundeterminedsignificanceprogressiontomultiplemyelomathroughmetaanalysisofgeodata AT maryampanahiazr characterizationofmonoclonalgammopathyofundeterminedsignificanceprogressiontomultiplemyelomathroughmetaanalysisofgeodata AT dexterhadley characterizationofmonoclonalgammopathyofundeterminedsignificanceprogressiontomultiplemyelomathroughmetaanalysisofgeodata AT donbenson characterizationofmonoclonalgammopathyofundeterminedsignificanceprogressiontomultiplemyelomathroughmetaanalysisofgeodata |