Masoumeh HASSANİ, Demet AKDENİZ, Tunay DOĞAN, Samuray TUNCER, Hülya YAZICI

UVEAL MALIGN MELANOMA HASTALARININ SERUM/ PLAZMASINDA YÜKSEK miR-454 EKSPRESYONU

Amaç: Uveal malign melanoma (UMM) kötü prognoza sahip, yüksek metastaz eğilimi gösteren ve erken teşhisi zor bir kanser türüdür. Bu nedenle bu hastalıkta non-invaziv diyagnostik ve prognostik biyobelirteçlere ihtiyaç duyulmaktadır. Çalışmamızda UMM tanısı almış hastalar ile sağlıklı kontrollerin periferik kan örneklerindeki miR-454 düzeyi ve ilgili molekülün diyagnostik ve prognostik bir biyobelirteç olma özelliği taşıyıp taşımadığı araştırılmıştır. Gereç ve Yöntem: Bu çalışma İstanbul Üniversitesi, İstanbul Tıp Fakültesi, Göz Hastalıkları Anabilim Dalı ile Onkoloji Enstitüsü’ne başvuran, 72 UMM’li hasta ve bu hasta grubu ile yaş, cinsiyet ve etnik köken açısından eşleştirilmiş 72 sağlıklı kontrolden oluşan bir katılımcı grubunun periferik kan örnekleri kullanılarak gerçekleştirilmiştir. Periferik kan örneklerine ait serum/plazmalardan cell free RNA (cfRNA) izolasyonu yapılarak miR-454 ifade düzeyi gerçek zamanlı Polimeraz Zincir Reaksiyonu (GZ-PZR) ile analiz edilmiştir. Referenas gene göre belirlenen miR-454 ekspresyon düzeyi hasta ve sağlıklı kontroller ile karşılaştırılarak değerlendirilmiştir. Bulgular: Uveal malign melanoma ve sağlıklı kontrol grupları arasında yapılan incelemede, miR-454 ifade düzeyinin sağlıklı kontrollere göre hasta grubunda 4,14 kat arttığı ve istatistiksel olarak anlamlı olduğu saptanmıştır. Çalışmada miR-454 ifade düzeyi ile sigara ve alkol kullanımı arasında anlamlı bir ilişki olduğu gösterilmiştir. Daha sonra miR-454’ün hedef mRNA’ları biyoinformatik araçlarla incelenmiş ve miR-454’ün kanserde tümör baskılayıcı ve onkogenik fonksiyonlara sahip olduğu anlaşılmıştır. Sonuç: Çalışmamız, daha önce çeşitli hücre hatlarında ve UMM tümör dokusunda yüksek ifade düzeyine sahip olduğu bildirilen miR-454’ün UMM hastalarının serum/plazmasında da yüksek düzeyde ifade edildiğini göstermiştir. Periferik kan dolaşımında, özellikle serum/plazmada araştırılan miR-454 ifade düzeyinin UMM’de diyagnostik ve prognostik biyobelirteç olarak kullanılabileceğini ve önemli bir terapötik hedef olarak değerlendirilebileceğini düşündürmektedir.

Anahtar Kelimeler:

Uveal Malign Melanoma, MikroRNA-454, periferik dolaşım, serum, plazma, biyobelirteç

HIGH LEVEL OF miR-454 EXPRESSION IN SERUM/PLASMA OF UVEAL MALIGN MELANOM PATIENTS

Objective: Uveal malignant melanoma (UMM) is a cancer type that has a poor prognosis and high metastasis tendency and is difficult to diagnose early. Therefore, non-invasive diagnostic and prognostic markers are needed in this disease. In the study, it was investigated the expression level of miR-454 in serum /plasma samples of UMM patients and also evaluated the feature of a diagnostic and prognostic biomarker of miR-454. Material and Method: This study was performed on peripheral blood samples from 72 patients with UMM and 72 healthy controls matched for age, sex, and ethnicity, who applied to Istanbul University, Istanbul Faculty of Medicine, Department of Ophthalmology and Oncology Institute. MicroRNA-454 expression level in cell-free RNA (cfRNA) isolated from serum/plasma was investigated by the Real-Time PCR (RT-PCR). The expression level of miR-454 determined according to the reference gene was evaluated by comparing it with patients and healthy controls. Results: It was found that the expression level of miR-454 increased 4.14 times in the patient group compared to the healthy controls, and it was statistically significant. In the study, it was shown that there is a significant relationship between miR-454 expression level and smoking and alcohol intake. When the mRNAs targeted by the miR-454 molecule were examined via bioinformatic tools and, it was understood that the relevant miRNA had a repressing feature and accordingly assumed the role of an oncogene. Conclusion: Our study has shown that miR-454, which was previously reported to have high expression levels in cell lines and UMM tumor tissue, is also found at high levels in the serum/plasma of UMM patients. The results suggest that miR-454 can be a diagnostic and prognostic biomarker in uveal malignant melanoma and can be considered as a important therapeutic target.

Keywords:

Uveal Malignant Melanoma, MicroRNA-454, peripheral circulation, serum, plasma, biomarker,

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