Expression patterns of eighteen genes involved in crucial cellular processes in the TP53 pathway in Multiple Myeloma

Abstract

Multiple myeloma (MM) is a malignant disease that causes abnormal immunoglobulin synthesis by bone marrow plasma cells. The relationship between MM and the TP53 pathway has not been fully elucidated in the literature. Investigation of the effect of the expression of genes in the TP53 pathway on the molecular pathogenesis and prognosis of multiple myeloma disease. We assessed the expression of 18 genes in the TP53 pathway in 48 MM patients and 31 healthy subjects by RT2-profiler PCR array technique, and investigated their possible association with the presence of cytogenetic aberrations. Twelve of the 18 genes (APAF1, ATM, BAX, CASP9, CDK4, CDKN1A, CDKN2A, E2F1, MCL1, MDM2, MDM4, PTEN) expression levels were found to be statistically up-regulated in MM patients compared to controls. The CDK4, CDKN1A and MCL1 genes were found to have remarkable diagnostic power distinguishing MM and healthy controls (AUC=0.89;AUC=0.86;AUC=0.77, respectively and p<0.001 for all three) via using Receiver operating characteristic (ROC) analysis. Overexpression of CDK4 and CDKN1A, which are involved in the cell cycle, and MCL1, which is an important gene in the anti-apoptotic process, were found to be excessively increased in MM patients compared to controls in terms of mRNA fold change. In addition, the high sensitivity of these genes found in the ROC analysis results suggests that they may be suggested as potential biomarkers for MM.

Keywords

• Multiple myeloma
• TP53 pathway
• RT² Profiler PCR Array
• Gene expression

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