Gene interaction network analysis in multiple myeloma detects complex immune dysregulation associated with shorter survival Journal Article
| Authors: | Simhal, A. K.; Maclachlan, K. H.; Elkin, R.; Zhu, J.; Norton, L.; Deasy, J. O.; Oh, J. H.; Usmani, S. Z.; Tannenbaum, A. |
| Article Title: | Gene interaction network analysis in multiple myeloma detects complex immune dysregulation associated with shorter survival |
| Abstract: | The plasma cell cancer multiple myeloma (MM) varies significantly in genomic characteristics, response to therapy, and long-term prognosis. To investigate global interactions in MM, we combined a known protein interaction network with a large clinically annotated MM dataset. We hypothesized that an unbiased network analysis method based on large-scale similarities in gene expression, copy number aberration, and protein interactions may provide novel biological insights. Applying a novel measure of network robustness, Ollivier-Ricci Curvature, we examined patterns in the RNA-Seq gene expression and CNA data and how they relate to clinical outcomes. Hierarchical clustering using ORC differentiated high-risk subtypes with low progression free survival. Differential gene expression analysis defined 118 genes with significantly aberrant expression. These genes, while not previously associated with MM, were associated with DNA repair, apoptosis, and the immune system. Univariate analysis identified 8/118 to be prognostic genes; all associated with the immune system. A network topology analysis identified both hub and bridge genes which connect known genes of biological significance of MM. Taken together, gene interaction network analysis in MM uses a novel method of global assessment to demonstrate complex immune dysregulation associated with shorter survival. © 2023, The Author(s). |
| Keywords: | adult; cancer survival; controlled study; middle aged; unclassified drug; major clinical study; genetics; dna repair; stat3 protein; progression free survival; apoptosis; immune system; multiple myeloma; gene expression; ubiquitin protein ligase; protein protein interaction; clinical assessment; cohort analysis; genetic association; gene product; immunoglobulin; protein interaction; high risk patient; survival time; janus kinase; geometry; gene interaction; interleukin 6; genomics; mitosis spindle; monocyte chemotactic protein 3; polo like kinase 2; univariate analysis; apc protein; interleukin 2 receptor alpha; cyclin dependent kinase 1; histone deacetylase 1; copy number variation; minichromosome maintenance protein 6; clinical outcome; gamma interferon receptor 1; procedures; immune dysregulation; protein interaction maps; gene knockdown; humans; prognosis; human; male; female; article; rna sequencing; hierarchical clustering; differential expression analysis; b cell maturation antigen; apolipoprotein b mrna editing enzyme catalytic polypeptide like; adp ribosyl cyclase/cyclic adp ribose hydrolase 1; gene network analysis; ada protein; alpha amidating enzyme; bin1 protein; ccno protein; dctn4 protein; ercc4 protein; gemin4 protein; gtf2h5 protein; inwardly rectifying potassium channel subunit kir2.1; izkf3 protein; kif1b protein; lats1 protein; mep1a protein; nfx1 protein; nitric oxide synthase trafficking; nol8 protein; p21 activated kinase 1; pdpn protein; protein jun; ring finger protein 115; sat1 protein; slamf7 protein; small proline rich protein 2 a; synuclein alpha interacting protein; wee1 g2 checkpoint kinase; ollivier ricci curvature |
| Journal Title: | Blood Cancer Journal |
| Volume: | 13 |
| ISSN: | 2044-5385 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2023-12-01 |
| Start Page: | 175 |
| Language: | English |
| DOI: | 10.1038/s41408-023-00935-2 |
| PUBMED: | 38030619 |
| PROVIDER: | scopus |
| PMCID: | PMC10687027 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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