Journal Article

Genome-wide identification of potential biomarkers in multiple myeloma using meta-analysis of mRNA and miRNA expression data

Gurvinder Kaur, Lingaraja Jena, Ritu Gupta, Amit Katiyar, Harpreet Singh, Lata Rani, Punit Kaur, Lalit Kumar, Atul Sharma

2021

Overview

Multiple myeloma (MM) is a plasma cell malignancy with diverse clinical phenotypes and molecular heterogeneity not completely understood. Differentially expressed genes (DEGs) and miRNAs (DEMs) in MM may influence disease pathogenesis, clinical presentation / drug sensitivities. But these signatures overlap meagrely plausibly due to complexity of myeloma genome, diversity in primary cells studied, molecular technologies/ analytical tools utilized. This warrants further investigations since DEGs/DEMs can impact clinical outcomes and guide personalized therapy. We have conducted genome-wide meta-analysis of DEGs/DEMs in MM versus Normal Plasma Cells (NPCs) and derived unified putative signatures for MM. 100 DEMs and 1,362 DEGs were found deranged between MM and NPCs. Signatures of 37 DEMs (‘Union 37’) and 154 DEGs (‘Union 154’) were deduced that shared 17 DEMs and 22 DEGs with published prognostic signatures, respectively. Two miRs (miR-16–2-3p, 30d-2-3p) correlated with survival outcomes. PPI analysis identified 5 topmost functionally connected hub genes ( UBC, ITGA4, HSP90AB1, VCAM1, VCP ). Transcription factor regulatory networks were determined for five seed DEGs with ≥ 4 biomarker applications ( CDKN1A, CDKN2A, MMP9, IGF1, MKI67 ) and three topmost up/ down regulated DEMs (miR-23b, 195, let7b/ miR-20a, 155, 92a). Further studies are warranted to establish and translate prognostic potential of these signatures for MM.

• Publisher: Springer Science and Business Media LLC,Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/114 / 631/67 / Biomarkers / Biomarkers, Tumor / Computational Biology / Data Mining / Datasets as Topic / Gelatinase B / Gene expression / Gene Expression Profiling / Gene Expression Regulation, Neoplastic / Gene Regulatory Networks / Genome-Wide Association Study / Genomes / Heterogeneity / Humanities and Social Sciences / Humans / Insulin-like growth factor I / Malignancy / Medicine / Meta-analysis / MicroRNAs / miRNA / multidisciplinary / Multiple Myeloma / Phenotypes / Plasma Cells / Prognosis / Protein Interaction Maps / Q / R / RNA, Messenger / RNA, Neoplasm / Science / Science (multidisciplinary)