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Expression and clinical significance of DCAF8 gene in multiple myeloma
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Abstract:
Objective: To search for potential pathogenic genes, disease diagnosis and prognosis related factors in multiple myeloma (MM) microarray datasets and clarify their mechanism. Methods: GSE13591 and Zhan Myeloma datasets were obtained, and the gene differential expression was analyzed by R language. Meta-analysis was performed based on merged datasets, and the TOP10 genes in median rank of P-value were screened. The mRNA expression of TOP10 genes in tumor cell lines were analyzed using CCLE database,and proteasome pathway related gene 8 (DCAF8) was screened. The mutation frequency of DCAF8 gene in each tumor cell lines was analyzed in cBioPortal database. Furthermore, the expression of DCAF8 protein in MM cell lines were detected by using WB. SPSS and Graph Pad software were employed to analyze the correlation between DCAF8 expression and clinical characteristics of MM patients. In addition, the receiver operating characteristic curve (ROC curve) and survival analysis were conducted according to the expression level of DCAF8. Finally, R clusterProfiler package and Metascape database were used to perform GO and KEGG functional enrichment analyses of DCAF8 interacting protein gene and co-expressed genes. Results: A total of 477 high expression genes were obtained from the intersection of the up-regulated genes of GSE13591 and Zhan Myeloma datasets. Meta-analysis of the above genes in the merged dataset was performed, the TOP10 genes in median P-value rank were HGF, AKAP1, TCTA, NEB, DCAF8, COPS6,MAP3K5, PON2, BAG1 and CD59. The analysis of CCLE database showed that the average expression level of DCAF8 was the highest in MM cell lines. The mutation frequency of DCAF8 gene in plasma cell myeloma ranked first among all tumor cell lines in cBioPortal database. The result of WB showed that the level of DCAF8 protein was increased significantly in a variety of MM cell lines compared with 293T control. The results showed that the expression of DCAF8 was positively correlated with the tumor load of MM patients, and the expression of DCAF8 in positive group of 1q21 amplification was significantly higher than that in negative group. The results of ROC curve based on GSE13591 and GSE16558 manifested that the expression level of DCAF8 had a good diagnostic value for MM (P<0.01). The survival analysis related to DCAF8 expression was conducted using the GSE2658, GSE4452 and GSE9782 datasets, and it showed that the level of DCAF8 expression was negatively correlated with the overall survival (OS) rate of MM patients. Protein interaction network showed that DCAF8 could interact with XPO1 protein directly. The GO and KEGG functional enrichment analysis showed that DCAF8 was related to proteasome function, spliceosome activity, histone acetylase activity, RNA transport, etc. Conclusion: DCAF8 is highly expressed in MM significantly, and its expression level can distinguish MM patients from normal people. Its expression is negatively correlated with the overall survival time of MM patients. Remarkably, DCAF8 is related to 1q21 amplification and could interact with XPO1 protein directly. Therefore, DCAF8 maybe a new biomarker of MM.
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Project Supported:
Project supported by the National Natural Science Foundation of China（No. 82170194，No. 81570181，No. 81920108006），the Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences（No. 2018PT31006，2018RC320012）
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