Açelya GÖKDENİZ YILDIRIM, Aydın DEMİRAY, Ali Can KOÇ, Hande ŞENOL, Arzu YAREN

Meme kanserli hastalarda 20 serum mirna’nın klinikopatolojik değişkenler ile ilişkisi

Amaç: MiRNA’ların meme kanseri patogenezinde rol oynadığının belirlenmesi, meme kanserinin tanı ve tedavisinde yararlı olabileceğini düşündürmektedir. Gereç ve yöntem: Toplanan 39 invaziv meme kanserli hasta serumundan mikroRNA’lar izole edildi ve cDNA’lara dönüştürüldü. Hastaların tanı anında ve tedavi sonrasında alınan kanlarından, 20 miRNA’nın (miR-105, miR-21, miR-141, miR-200a, miR-200b, miR-200c, miR-203, miR-210, miR-375, miR-34a, miR-133a, miR-155, miR-139-5p, miR-143, miR-145, miR-365, miR-299-5p, miR-411, miR-452 ve miR-17) serum düzeyleri analiz edildi. Bulgular: Analiz sonuçlarında, miR-200c (p=0.030), miR-375 (p=0.045), miR-34a’nın (p=0.042) serum düzeyleri lokal ileri/metastatik grupta anlamlı olarak yüksek saptandı. miR-141’in (p=0.062) serum seviyesi lenf nodu tutulumu pozitif hastalarda daha düşük gözlenirken, miR-133a (p=0.037) seviyelerinin aynı hasta grubunda daha yüksek olduğu tespit edildi. MiR-105 (p=0.015), miR-203 (p=0.015), miR-375 (p=0.033), miR-145 (p=0.025) serum seviyelerinin PR negatif grupta belirgin yüksek olduğu, aynı şekilde miR-105 (p=0.053) seviyelerinin ER negatif grupta yüksek olduğu görüldü. Her 2 pozitif hastalarda miR-375 ve miR-133a seviyelerinin yüksekliği dikkat çekti (p=0.037 ve p=0.014, sırasıyla). MiR-143 (p=0.009) ve miR-145 (p=0.017) seviyelerinin ki-67 indeksi >%20 olan hasta grubunda daha yüksek olduğu ve bu miRNA’ların ki-67 indeksi ile korelasyon gösterdiği gözlendi (p=0.007; p=0.015, sırasıyla). Moleküler alt gruplara göre ayrılan hastalardan luminal B grubunda olanlarda 2 miRNA’nın (miRNA-133a (p=0.018) ve miRNA-139-5p (p=0.004)) anlamlı olarak daha yüksek olduğu saptandı. Çalışılan miRNA’lardan 9 tanesinin (miRNA-105 (p=0.0001), miRNA-21 (p=0.001), miRNA-141 (p=0.041), miRNA-200a (p=0.003), miRNA-200b (p=0.0001), miRNA-200c (p=0.0001), miRNA-203 (p=0.0001), miRNA-34a (p=0.0001), miRNA-452 (p=0.018)) tedavi sonrasında anlamlı olarak arttığı, 5 tanesinin (miRNA-155 (p=0.0001), miRNA-143 (p=0.0001), miRNA-145 (p=0.0001), miRNA-365 (p=0.0001), miRNA-299-5p (p=0.0001)) tedavi sonrasında anlamlı olarak azaldığı görüldü. Sonuç: Sonuçlarımızın, invaziv meme kanserinin takibi ve prognozunu değerlendirmede yol gösterici olabileceğini düşünmekteyiz.

Anahtar Kelimeler:

İnvaziv meme kanseri, dolaşan miRNA, moleküler subtipler, klinik ve patolojik değişkenler

Association between 20 serum mirnas and clinicopathological variables in patients with breast cancer

Purpose: Determining microRNAs in breast cancer pathogenesis suggests that it may be beneficial for diagnosis and treatment. Materials and methods: Patients serum were collected and microRNAs were isolated. Then microRNAs was converted to cDNA. After that, investigated serum levels of 20 microRNAs (miR-17, miR-21, miR-34a, miR-105, miR-133a, miR-139-5p, miR-141, miR-143, miR-145, miR-155, miR-200a, miR-200b, miR-200c, miR-203, miR-210, miR-299-5p, miR-365, miR-375, miR-411, miR-452) in 39 patients with invasive breast cancer were analyzed before and after treatment. Results: In the analysis results, it is detected that serum levels of miR-200c, miR-375, miR-34a were markedly higher in the local advanced/metastatic group. MiR-141 levels was lower in patients with positive lymph node involvement, whereas miR-133a levels were higher in the same patient group. miR-105, miR-203, miR-375, miR-145 serum levels were markedly higher in the progesterone receptor negative group, likewise miR-105 levels were high in the estrogen receptor negative group. The high levels of miR-375 and miR-133a were noticeable in human epidermal growth factor receptor-2 positive patients. MiR-143 and miR-145 levels were observed higher in the patient with a ki-67 index >20%. It was found that 2 miRNAs (miR-133a and miR-139-5p) were markedly higher in patients in the luminal B group, which were separated by molecular subgroups. Nine of miRNAs that evaluated (miR-21, miR-34a, miR-105, miR-141, miR-200a, miR-200b, miR-200c, miR-203, miR-452) significantly increased and 5 of the miRNAs (miR-145, miR-365, miR-155, miR-143, miR-299-5p) were significantly reduced post-treatment. Conclusion: We think that miRNAs may help in evaluating the follow-up and prognosis of invasive breast cancer.

Keywords:

Invasive breast cancer, circulating miRNA, molecular subtypes, clinical and pathological variables,

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