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. 2023 Mar 28;12(7):1029.
doi: 10.3390/cells12071029.

The TT Genotype of the KIAA1524 rs2278911 Polymorphism Is Associated with Poor Prognosis in Multiple Myeloma

Aneta Szudy-Szczyrek  1 , Radosław Mlak  2 , Marcin Mazurek  3 , Tomasz Krajka  4 , Sylwia Chocholska  1 , Paulina Bitkowska  1 , Marta Jutrzenka  5 , Michał Szczyrek  6 , Iwona Homa-Mlak  3 , Andrzej Krajka  7 , Teresa Małecka-Massalska  3 , Marek Hus  1
Affiliations

The TT Genotype of the KIAA1524 rs2278911 Polymorphism Is Associated with Poor Prognosis in Multiple Myeloma

Aneta Szudy-Szczyrek et al. Cells. .

Abstract

Background: The KIAA1524 gene encodes an oncoprotein, CIP2A, which inhibits the phosphorylation of the Akt kinase B, stabilizes the c-Myc protein, and, through that, promotes cancerogenesis. An increase in CIP2A expression has been observed in numerous solid tumors and hematologic malignancies, including multiple myeloma (MM). The aim of our study was to evaluate the clinical impact of the functional single nucleotide polymorphisms (SNP) of the KIAA1524 gene (rs2278911, 686C > T) in MM patients.

Methods: The study group consisted of 128 patients with de novo MM. EDTA venous blood samples were collected prior to the treatment. The SNPs were analyzed by Real-Time PCR with the use of specific Taqman probes.

Results: Multivariable analysis revealed that variables independently associated with shorter progression-free survival (PFS) included thrombocytopenia, delTP53 and IGH/CCND1 translocation and the TT genotype of the KIAA1524 gene (686C > T) (median PFS: 6 vs. 25 months; HR = 7.18). On the other hand, autologous haematopoietic stem cell transplantation (AHSCT) was related to a lower risk of early disease progression. Moreover, light chain disease, International Staging System (ISS) 3, poor performance status, hypoalbuminemia, IGH/FGFR3 translocation and the TT genotype of the KIAA1524 gene (686C > T) were independent prognostic factors associated with shorter overall survival (OS) (median OS: 8 vs. 45 months; HR = 7.08).

Conclusion: The evaluation of the SNP 686C > T of the KIAA1524 gene could be used as a diagnostic tool in MM patients at risk of early disease progression and death.

Keywords: CIP2A; MYC; molecular biomarkers; multiple myeloma; polymorphism; prognosis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Kaplan–Meier curves presenting the influence of KIAA gene genotypes on progression-free survival (A) and overall survival (B).
Figure 2
Figure 2
Forest plot showing the results of multivariate analysis for progression-free survival (A) and overall survival (B).
Figure 3
Figure 3
Box–whisker graph presenting a comparison of expression of the KIAA1524 gene depending on genotypes of the SNP of this gene (A). Distribution plot presenting correlation between expression of KIAA1524 gene expression of the MYC gene (B).
Figure 4
Figure 4
Heat map presenting correlation matrix, including CIP2A/KIAA1524 and selected genes involved in the biology or pathomechanism of MM, created based on data retrieved from the CoMMpass project.
Figure 5
Figure 5
Heat map presenting correlation matrix including 30 genes demonstrating the strongest correlation with CIP2A/KIAA1524, created based on data retrieved from the CoMMpass project.
See this image and copyright information in PMC

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