Low TYROBP expression predicts poor prognosis in multiple myeloma

被引:5
作者
Luo, Hong [1 ,2 ]
Pan, Chengyun [1 ]
Wang, Li [1 ,2 ]
Zheng, Lin [1 ,2 ]
Cao, Shuyun [1 ,2 ]
Hu, Xiuying [1 ]
Hu, Tianzhen [1 ]
Zhao, Naiqin [1 ]
Shang, Qin [1 ]
Wang, Jishi [1 ,2 ,3 ]
机构
[1] Guizhou Med Univ, Affiliated Hosp, Dept Hematol, Guiyang 550004, Peoples R China
[2] Guizhou Med Univ, Med Sch, Dept Clin, Guiyang 550004, Peoples R China
[3] Soochow Univ, Affiliated Hosp 1, Natl Clin Res Ctr Hematol Dis, Suzhou 215006, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
Biomarker; TYROBP; Multiple myeloma; Prognosis; Adhesion; Migration; DAP12; INFLAMMATION;
D O I
10.1186/s12935-024-03304-6
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background Multiple myeloma (MM) is the second most common refractory hematologic cancer. Searching for new targets and prognostic markers for MM is significant.Methods GSE39754, GSE6477 and GSE24080 were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) in MM versus healthy people from GSE39754 and GSE6477 were screened using limma package, and MM-related module genes were chosen with the use of Weighted gene co-expression network analysis (WGCNA), and the two were intersected using ggVennDiagram for obtaining MM-related DEGs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were carried out. Then, protein-protein interactions (PPI) analysis in String database was used to obtain hub genes, while prognosis was analyzed by survival package in GSE24080. Receiver operating characteristic (ROC) curve was adopted for evaluating diagnostic value of hub genes. Besides, univariable/multivariable Cox regression were employed to screen independent prognostic biomarkers. Gene set enrichment analysis (GSEA) was used to find possible mechanism. Finally, western-blotting and reverse transcription-polymerase chain reaction (RT-PCR) verify TYROBP expression within MM and healthy people. We performed cell adhesion and transwell assays for investigating TYROBP function in MM cell adhesion and migration.Results Through differential analyses, 92 MM-related DEGs were obtained. 10 hub genes were identified by PPI and CytoHubba. Their diagnostic and prognostic significance was analyzed. Down-regulation of genes like TYROBP, ELANE, MNDA, and MPO related to dismal MM prognosis. Upon univariable/multivariable Cox regression, TYROBP independently predicted MM prognosis. GSEA pathway was enriched, indicating that TYROBP expression affected MM development via cell adhesion molecular pathway. Upon Western-blotting and RT-PCR assays, TYROBP expression among MM patients decreased relative to healthy donors. Cell adhesion and transwell migration assays revealed increased MM cell adhesion and decreased migration upon TYROBP up-regulation.Conclusion In summary, TYROBP is a potential prognostic marker for MM.
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页数:14
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