MDR1 promoter metilasyonu temozolomid direncini etkiler mi? Glioblastomlu hastalarda klinik çalışma

Öz

Amaç: Çoklu ilaç direnci 1 (MDR1) gen ekspresyonu ve epigenetik durumu, glioblastomun (GB) kemoterapötik direncinde önemli bir faktör olabilir. Bu çalışmanın amacı, MDR1 promoter metilasyon durumunun, hastanın sağkalımı, kemoterapi direnci ve hastalığın tekrarlaması ile ilgili olarak GB tümör dokusu üzerindeki etkisini analiz etmektir.
Gereç ve yöntem: …. Üniversitesi Tıp Fakültesi Beyin Cerrahisi Anabilim Dalı'nda GB tanısı ile ameliyat edilen 36 hastanın verileri incelendi. Hastaların klinik bilgileri ve tümör dokularının MDR1 metilasyon durumu, hastanın sağkalımı, kemoterapi direnci ve tümör nüksü üzerindeki etkilerine yönelik karşılaştırıldı.
Bulgular: MDR1’nin metile olduğu GB'li hastalarda istatistiksel olarak anlamlı (p<0,001) daha kısa sağkalım süreleri saptandı. Metile tümör dokusu olan hastaların %25'inde ve hemi-metile tümör dokusu olan hastaların %39,3'ünde erken rekürrens saptandı.
Sonuç: GB'li tüm hastalarda standart kemoterapötikleri kullanmak yerine, GB'nin genetik heterojenliği nedeniyle tümörün epigenomik özellikleri ve ekspresyon durumu dikkate alınarak dokuya özgü ilaçlar seçilmelidir. Bu, literatürdeki MDR1 promoter metilasyonu ile GB'nin klinik verileri arasındaki ilişkiyi gösteren ilk çalışmadır.

Anahtar Kelimeler

• Kemoterapötik direnç
• glioblastoma
• metilasyon
• çoklu ilaç direnci geni 1

Does MDR1 promoter methylation affect temozolomide resistance? A clinical study in patients with glioblastoma

Öz

Purpose: The multidrug resistance 1 (MDR1) gene expression and its epigenetic status may be an important factor in the chemotherapeutic resistance of glioblastoma (GB). The aim of this study was to analyze the effect of the MDR1 promoter methylation status on GB tumor tissue related with patient survival, chemotherapy resistance, and recurrence of the disease.
Materials and methods: Thirty-six patients underwent surgery for GB at the Neurosurgery Department of Ankara University School of Medicine. The patients’ clinical information and the MDR1 methylation status of the tumor tissues was compared to determine the effects on patient survival, chemotherapy resistance, and tumor recurrence.
Results: Patients with MDR1 methylated GB had statistically significantly (p<0.001) shorter survival times. Early recurrence was detected in 25% of the patients with unmethylated tumor tissues and in 39.3% with hemimethylated tumor tissues.
Conclusion: Instead of using the standard chemotherapeutics in all the patients with GB, tissue-specific medications must be chosen while taking into consideration the epigenomic characteristics and expression status of the tumor because of the genetic heterogeneity of GB. This is the first study to show the association between MDR1 promoter methylation and the clinical data of GB in the literature.

Anahtar Kelimeler

• Chemotherapeutic resistance
• glioblastoma
• methylation
• multidrug resistance 1

Kaynakça

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