Evaluation of miR-145 and miR-146a as potential biomarkers for diagnosis of Myelodysplastic Syndrome

Yıl 2022, Cilt: 5 Sayı: 2, 61 - 66, 27.06.2022

Seda Süsgün Onur Baykara Emrah Yücesan R. Dilhan Kuru Başak Aslaneli Çakmak Ayşegül Yabacı Şeniz Öngören Ayhan Deviren Yelda Tarkan Argüden

Öz

Objective: Myelodysplastic syndromes (MDS) are a group of heterogeneous hematopoietic stem cell disorders characterized by ineffective hematopoiesis, bone marrow dysplasia, and peripheral cytopenias. microRNAs (miRNAs) are small non-coding RNAs that play key roles in post-transcriptional regulation of gene expression and have been determined potential in disease diagnostics and therapeutics owing to their stability. Recent evidence suggests that haploinsufficiency of the miR-145 and miR-146a, encoded from 5q Common Deleted Region (CDR) may contribute to the phenotype in MDS. Although, interstitial del(5q) is the most common chromosomal abnormality in MDS, these findings are inconsistent in Turkish patients. Therefore, we aimed to investigate assess the diagnostic value of miR-145/miR-146a and their relation with del(5q) or monosomy 5 in MDS. Methods: In order to determine the association between del(5q) and expression miR-145/miR-146a, conventional cytogenetics (CC), FISH, and qRT-PCR methods were performed for 24 patients with MDS and 20 healthy individuals. Additionally, ROC curves were generated to evaluate putative diagnostic value of miRNAs. Results: Cytogenetic examination revealed clonal cytogenetic abnormalities in 43.4% of cases. miR-146a decreased in 23 of 24 patients regardless of chromosome 5 abnormalities (p<0.0001), expression level of miR-145 was statistically nonsignificant. miR-146a levels performed well as a diagnostic biomarker, discriminating MDS patients from controls with an area under the ROC curve (AUC) of 0.942, 83.3% sensitivity. Conclusion: miR-146a may be used as a biomarker in diagnosis of MDS and may help to identify new treatment targets. In addition, we suggest that CC and FISH methods should be performed together in MDS.

Anahtar Kelimeler

Myelodysplastic syndrome, diagnostic biomarkers, miR-146a, ROC curve

Destekleyen Kurum

This work was supported by the grants of Scientific Research Projects Coordination Unit of Istanbul University (no: 24461) and Turkish Society of Hematology (no: 2017/1).

Miyelodisplastik Sendrom tanısında miR-145 ve miR-146a’nın potansiyel biyobelirteç olarak değerlendirilmesi

Öz

Amaç: Miyelodisplastik sendrom (MDS), verimsiz hematopoez, kemik iliği displazisi ve periferik sitopeni ile karakterize edilen heterojen bir grup hematopoetik kök hücre bozukluğudur. mikroRNA'lar (miRNA'lar), gen ifadesinin post-transkripsiyonel düzenlenmesinde kilit rol oynayan küçük kodlamayan RNA’lardır ve stabiliteleri sayesinde hastalık tanısında ve tedavisinde potansiyelleri belirlenmiştir. Son çalışmalar, 5q Yayın Delesyon Bölgesi’nden (YDB) kodlanan miR-145 ve miR-146a'nın haplo-yetmezliğinin MDS'deki fenotipe katkıda bulunabileceğini düşündürmektedir. MDS'de en sık gözlenen kromozom anomalisi interstisyel del(5q) olmasına rağmen, bu bulgular Türkiye popülasyonundaki örnekler ile tutarsızdır. Bu nedenle, MDS'de miR-145/miR-146a'nın tanısal kullanım değerini ve bu miRNA’ların del(5q) ve/veya monozomi 5 ile ilişkisini değerlendirmeyi amaçladık. Yöntem: del(5q) ile miR-145/miR-146a ekspresyonu arasındaki ilişkiyi belirlemek için MDS'li 24 hasta ve 20 sağlıklı kontrol için konvansiyonel sitogenetik (CC), FISH ve qRT-PCR yöntemleri uygulanmıştır. Ek olarak, miRNA'ların tanısal değerini değerlendirmek için ROC eğrileri oluşturulmuştur. Bulgular: Sitogenetik incelemeler, vakaların %43,4'ünde klonal sitogenetik anomali olduğunu gösterdi. miR-146a ifadesi, 5. kromozom anomalilerinden bağımsız olarak 24 hastanın 23'ünde azalmaktaydı (p<0,0001), miR-145'in ekspresyon düzeyi istatistiksel olarak anlamlı değildi. miR-146a ifade seviyesi, MDS hastalarını kontrollerden ayırmada 0,942 ROC eğrisi altında kalan alan (AUC) değeri ve %83,3 hassasiyet değeri ile iyi bir tanısal biyobelirteç performansı sergiledi. Sonuç: miR-146a, MDS tanısında bir biyobelirteç olarak kullanılabilir ve yeni tedavi hedeflerinin belirlenmesine yardımcı olabilir. Ayrıca MDS'de CC ve FISH yöntemlerinin birlikte yapılmasını öneriyoruz.

Anahtar Kelimeler

Miyelodisplastik sendrom, tanısal biyobelirteç, miR-146a, ROC eğrisi

Kaynakça

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