Identification of key biomarkers associated with cell adhesion in multiple myeloma by integrated bioinformatics analysis

Background: Multiple Myeloma (MM) is a hematologic malignant disease whose underlying molecular mechanism has not yet fully understood. Generally, cell adhesion plays an important role in MM progression. In our work, we intended to identify key genes involved in cell adhesion in MM.

Methods: First, we identified differentially expressed genes (DEGs) from the mRNA expression profiles of GSE6477 dataset using GEO2R with cut-off criterion of p < 0.05 and [logFC] ≥ 1. Then, GO and KEGG analysis were performed to explore the main function of DEGs. Moreover, we screened hub genes from the protein-protein interaction (PPI) network analysis and evaluated their prognostic and diagnostic values by the PrognoScan database and ROC curves. Additionally, a comprehensive analysis including clinical correlation analysis, GSEA and transcription factor (TF) prediction, pan-cancer analysis of candidate genes was performed using both clinical data and mRNA expression data.

Results: First of all, 1383 DEGs were identified. Functional and pathway enrichment analysis suggested that many DEGs were enriched in cell adhesion. 180 overlapped genes were screened out between the DEGs and genes in GO terms of cell adhesion. Furthermore, 12 genes were identified as hub genes based on a PPI network analysis. ROC curve analysis demonstrated that ITGAM, ITGB2, ITGA5, ITGB5, CDH1, IL4, ITGA9, and LAMB1 were valuable biomarkers for the diagnosis of MM. Further study demonstrated that ITGA9 and LAMB1 revealed prognostic values and clinical correlation in MM patients. GSEA and transcription factor (TF) prediction suggested that MYC may bind to ITGA9 and repress its expression and HIF-1 may bind to LAMB1 to promote its expression in MM. Additionally, pan-cancer analysis showed abnormal expression and clinical outcome associations of LAMB1 and ITGA9 in multiple cancers.

Conclusion: In conclusion, ITGA9 and LAMB1 were identified as potent biomarkers associated with cell adhesion in MM.