Exploring the Molecular Mechanisms and Shared Genetic Characteristics of Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma

Author:

Fu Yuanjing1,Gu Weiying1,Lin Yan1,Cao Yang1,Luo Jiaru1,Zheng Zhuojun1,Liu Yan1

Affiliation:

1. The Third Affiliated Hospital of Soochow University

Abstract

Abstract

Monoclonal gammopathy of undetermined significance (MGUS) serves as a precursor to multiple myeloma (MM), with a subset of MGUS cases advancing to MM each year. Despite extensive research, the mechanisms driving this progression are not yet fully understood. Leveraging transcriptomic data from the Gene Expression Omnibus (GEO) database, this study conducted an analysis of differentially expressed genes (DEGs) between MGUS and MM. Weighted gene co-expression network analysis (WGCNA) was utilized to pinpoint significant gene modules linked to disease progression. Univariate Cox analysis and LASSO regression were employed to identify genes associated with MM prognosis. Immune scores and immune cell proportions were calculated using ESTIMATE and CIBERSORT tools. A total of 961 DEGs related to MM and 355 DEGs associated with MGUS were identified. Cross-analysis revealed 12 intersecting genes, with four (DAP3, HIST1H1C, MRPL4, and UBE2S) as core genes. The MGUSscore effectively stratified MM patients into high-risk and low-risk groups, with the high-risk group showing significantly shorter overall survival (P < 0.05). Core genes were closely linked to immune cell infiltration. A ceRNA network identified 68 miRNAs and 10 lncRNAs related to core genes. DAP3, HIST1H1C, MRPL4, and UBE2S are potential therapeutic targets for MM.

Publisher

Springer Science and Business Media LLC

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