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Identification and validation of aging-related genes in patients with multiple myeloma
Huajing Liu1,2, Senhua Song3, Yingtao Wu1
1Department of Laboratory Medicine, General Hospital of Central Theater Command, Wuhan, Hubei 430000, P.R. China.
Abstract:
This study aimed to identify and validate aging-related genes (ARGs) implicated in multiple myeloma (MM), thereby advancing the understanding of the molecular mechanisms underlying the disease. mRNA expression data were retrieved from the Gene Expression Omnibus, and used as a training set to identify ARGs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted to explore the functional roles of the ARGs in MM. Candidate genes identified through least absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine recursive feature elimination (SVM-RFE) were compared using a Venn diagram, which revealed the overlap between the genes identified by the two algorithms. A receiver operating characteristic curve was generated based on the screening results. The candidate genes were further validated using the GSE39754 and GSE5900 datasets. Real-time quantitative polymerase chain reaction (RT-qPCR) was employed to validate the mRNA expression of key genes. Compared to normal individuals, patients with MM exhibited differential expression of 19 genes, of which 5 were upregulated and 14 downregulated. A total of 6 candidate genes (TXN, JUN, FOS, HIF1A, CAT and KCNA3) were identified through LASSO regression and SVM-RFE screening. Among them, TXN exhibited the most significant differential expression, suggesting its potential as a diagnostic biomarker for MM. In addition, in vitro RT-qPCR analysis confirmed that the mRNA levels of TXN in MM cells aligned with the bioinformatics findings, showing higher expression compared to normal B-lymphocyte cell lines. In conclusion, this study identified age-associated molecular patterns in MM and highlighted the diagnostic potential of TXN, offering novel insights for clinical applications in MM.
Insights
This study identified 6 aging-related genes in multiple myeloma (MM), with TXN showing significant differential expression. TXN holds potential as a diagnostic biomarker for MM, offering new clinical insights.
Area of Science:
- Genomics
- Molecular Biology
- Oncology
Background:
- Multiple myeloma (MM) is a hematological malignancy with complex molecular underpinnings.
- Aging-related genes (ARGs) play a role in various diseases, but their specific involvement in MM requires further elucidation.
Purpose of the Study:
- To identify and validate ARGs associated with multiple myeloma (MM).
- To explore the functional roles of these ARGs in MM pathogenesis.
- To identify potential diagnostic biomarkers for MM.
Main Methods:
- Utilized Gene Expression Omnibus (GEO) data for ARG identification.
- Employed LASSO logistic regression and SVM-RFE for candidate gene selection.
- Validated candidate genes using independent datasets (GSE39754, GSE5900) and RT-qPCR.
Main Results:
- Identified 19 differentially expressed genes in MM patients compared to normal individuals.
- Selected 6 candidate ARGs (TXN, JUN, FOS, HIF1A, CAT, KCNA3) via LASSO and SVM-RFE.
- TXN showed the most significant differential expression and was validated in MM cells via RT-qPCR.
Conclusions:
- Discovered age-associated molecular patterns in multiple myeloma.
- Highlighted the potential of TXN as a diagnostic biomarker for MM.
- Provided novel insights for potential clinical applications in MM management.
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