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

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          Abstract

          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.

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          Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing

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            NCBI GEO: archive for functional genomics data sets—update

            The Gene Expression Omnibus (GEO, http://www.ncbi.nlm.nih.gov/geo/) is an international public repository for high-throughput microarray and next-generation sequence functional genomic data sets submitted by the research community. The resource supports archiving of raw data, processed data and metadata which are indexed, cross-linked and searchable. All data are freely available for download in a variety of formats. GEO also provides several web-based tools and strategies to assist users to query, analyse and visualize data. This article reports current status and recent database developments, including the release of GEO2R, an R-based web application that helps users analyse GEO data.
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              International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma.

              This International Myeloma Working Group consensus updates the disease definition of multiple myeloma to include validated biomarkers in addition to existing requirements of attributable CRAB features (hypercalcaemia, renal failure, anaemia, and bone lesions). These changes are based on the identification of biomarkers associated with near inevitable development of CRAB features in patients who would otherwise be regarded as having smouldering multiple myeloma. A delay in application of the label of multiple myeloma and postponement of therapy could be detrimental to these patients. In addition to this change, we clarify and update the underlying laboratory and radiographic variables that fulfil the criteria for the presence of myeloma-defining CRAB features, and the histological and monoclonal protein requirements for the disease diagnosis. Finally, we provide specific metrics that new biomarkers should meet for inclusion in the disease definition. The International Myeloma Working Group recommends the implementation of these criteria in routine practice and in future clinical trials, and recommends that future studies analyse any differences in outcome that might occur as a result of the new disease definition.
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                Author and article information

                Contributors
                punitkaur1@hotmail.com
                drritugupta@gmail.com
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                26 May 2021
                26 May 2021
                2021
                : 11
                : 10957
                Affiliations
                [1 ]GRID grid.413618.9, ISNI 0000 0004 1767 6103, Bioinformatics Facility, Centralized Core Research Facility, , All India Institute of Medical Sciences, ; Ansari Nagar, New Delhi, 110029 India
                [2 ]GRID grid.19096.37, ISNI 0000 0004 1767 225X, ICMR-AIIMS Computational Genomics Centre, Division of Biomedical Informatics, , Indian Council of Medical Research, ; Ansari Nagar, New Delhi, 110029 India
                [3 ]GRID grid.413618.9, ISNI 0000 0004 1767 6103, Department of Biophysics, , All India Institute of Medical Sciences, ; Ansari Nagar, New Delhi, 110029 India
                [4 ]GRID grid.413618.9, ISNI 0000 0004 1767 6103, Laboratory Oncology Unit, Dr B. R. A. Institute Rotary Cancer Hospital, , All India Institute of Medical Sciences, ; New Delhi, 110029 India
                [5 ]GRID grid.413618.9, ISNI 0000 0004 1767 6103, Genomics Facility, Centralized Core Research Facility, , All India Institute of Medical Sciences, ; Ansari Nagar, New Delhi, 110029 India
                [6 ]GRID grid.413618.9, ISNI 0000 0004 1767 6103, Department of Medical Oncology, Dr B. R. A. Institute Rotary Cancer Hospital, , All India Institute of Medical Sciences, ; Ansari Nagar, New Delhi, 110029 India
                Article
                90424
                10.1038/s41598-021-90424-y
                8154993
                34040057
                b5ebccb7-e0cb-4d7f-bd0f-7eaa85855621
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 20 December 2020
                : 29 April 2021
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001407, Department of Biotechnology, Ministry of Science and Technology, India;
                Award ID: BT/ PR7136 /MED /30/901/2012 and BT/MED/30/SP11006/2015
                Award Recipient :
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                © The Author(s) 2021

                Uncategorized
                cancer,computational biology and bioinformatics
                Uncategorized
                cancer, computational biology and bioinformatics

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