Decreased GADD45A gene expression level in MGUS

Abstract

Purpose: Monoclonal gammopathy of undetermined significance (MGUS) is a plasma cell dyscrasia. It is known that MGUS has an increased risk of progression to multiple myeloma (MM), and prepares the ground for diseases such as Waldenstrom macroglobulinemia (WM), non-Hodgkin lymphoma, and chronic lymphocytic leukemia (CLL). Our study aimed to evaluate whether some important p53 pathway genes differ in terms of expression between MGUS and healthy individuals. Materials and methods: Bone marrow was collected from eight healthy individuals and eight individuals diagnosed with MGUS, and RNA samples were isolated. The expression levels of various genes involved in the p53 pathway were compared using an RT2-profiler PCR array. β-Actin housekeeping gene expression level was used for normalization. Pearson’s Correlation and Receiver Operating Characteristic (ROC) analyses were conducted. Results: Among the genes whose expression levels were examined in this study, it was determined that the expression level of only the GADD45A gene decreased significantly in the MGUS group compared to the control group (p=0.027). Pearson’s correlation data showed that GADD45A gene expression was highly correlated with 12 of the other genes (APAF1, CDK4, PCNA, BAX, CDKN2A, CASP9, CHEK2, MDM2, RB1, P53, BCL2, CHEK1) examined in the p53 pathway (r>0.7). In addition, according to the ROC analysis, GADD45A was detected to have strong discrimination power between MGUS and healthy individuals (AUC=0.797 and p=0.015). Conclusion: The decreased expression of the GADD45A gene in the MGUS group compared to the control group may be useful as a new biomarker to detect the development of MGUS.

Keywords

• MGUS
• p53 pathway
• GADD45A

MGUS'ta azalmış GADD45A gen ekspresyonu seviyesi

Abstract

Amaç: Belirsiz öneme sahip monoklonal gamopati (MGUS), bir plazma hücre diskrazisidir. MGUS'un Multipl miyelom’a (MM) ilerleme riskini artırdığı, ayrıca Waldenstrom makroglobulinemi (WM), non-Hodgkin lenfoma ve kronik lenfositik lösemi (KLL) gibi hastalıklara zemin hazırladığı bilinmektedir. Çalışmamızda bazı önemli p53 yolağı genlerinin MGUS ve sağlıklı bireylerde ekspresyon açısından farklılık gösterip göstermediğini değerlendirmeyi amaçladık. Gereç ve yöntem: Çalışma için 8 sağlıklı ve 8 MGUS tanılı bireyden kemik iliği toplandı ve RNA örnekleri izole edildi. p53 yolağında yer alan çeşitli genlerin (BAX, CDKN2A, APAF1, ATM, ATR, CASP9, CDK4, CDKN1A, CHEK2, E2F1, E2F3, MCL1, MDM2, MDM4, PTEN, RB1, P53, BCL2, CHEK1, GADD45A, PCNA, PTX3) ekspresyon seviyeleri, RT2-profiler PCR array yöntemiyle karşılaştırıldı. Normalizasyon için β-Aktin gen ekspresyon seviyesi kullanıldı. Pearson Korelasyon ve Receiver Operating Characteristic (ROC) analizleri yapıldı. Bulgular: Bu çalışmada ekspresyon seviyeleri incelenen genlerden sadece GADD45A geninin ekspresyon seviyesinin kontrol grubuna göre MGUS'ta anlamlı olarak azaldığı belirlendi (p=0,027). Pearson korelasyon verileri, GADD45A gen ekspresyonunun, p53 yolağında incelenen diğer 12 gen (APAF1, CDK4, PCNA, BAX, CDKN2A, CASP9, CHEK2, MDM2, RB1, P53, BCL2, CHEK1) ile yüksek oranda ilişkili olduğunu gösterdi (r>0,7). Ayrıca ROC analizine göre GADD45A'nın MGUS ile sağlıklı bireyler arasında güçlü bir ayrım gücüne sahip olduğu saptandı (AUC=0,797 ve p=0,015). Sonuç: GADD45A geninin MGUS grubunda kontrol grubuna göre azalmış ekspresyonu, MGUS gelişimini saptamak için yeni bir biyobelirteç olarak faydalı olabilir.

Keywords

• MGUS
• p53 yolağı
• GADD45A

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