Meme kanseri gelişiminde miRNA' ların rolünün araştırılması
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Date
2012
Authors
Ertürk, Elif
Journal Title
Journal ISSN
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Publisher
Uludağ Üniversitesi
Abstract
Meme kanseri, dünyada kadınlar arasında en sık görülen kanser türüdür. Son yıllarda mikroRNA' ların işlevlerinin ve kanserdeki rollerinin anlaşılmaya başlanması, hem kanserin moleküler patolojisinin anlaşılmasında hem de yeni moleküler hedefe yönelik tedavilerin geliştirilmesinde umut olmuştur.Çalışmada erken yaş ya da aile öyküsü olan ve BRCA1/2 genlerinin mutasyon analizleri gerçekleştirilen toplam 60 meme kanserli hastanın tümör doku örnekleri ve ilgili hastaların 20' sinin normal doku örneklerinde; meme kanser gelişiminde diagnostik, prognostik ve ilaç direnci ile ilgili önemi olan 14 miRNA' nın (miR-21, miR-155, miR-145, let-7a, miR-10b, miR-125b, miR-221, miR-222, miR-205, miR-126, miR-206, miR-200c, miR-31, miR-335) ekspresyon analizleri gerçekleştirildi. Elde edilen veriler; Independent Samples T Testi, Kaplan Meier, Doğrusal Regresyon, Pearson Chi-Square ve Fisher's Exact Test' leri kullanılarak değerlendirildi. BRCA mutasyonu belirlenen erken yaş ve/veya ailesel meme kanserli hastalarda let-7a ve miR-335 ekspresyon seviyelerinde azalış belirlendi. Aynı zamanda azalışın, tümör büyümesi ve metastaz ile ilişkisi değerlendirilerek istatistiksel olarak anlamlı bulundu (p=0.044, p=0.022).Elde edilen bulgular ışığında; BRCA mutasyonu taşıyan, kötü prognoz potansiyeli olan erken yaş ve ailesel meme kanserli hastalarda let-7a ve miR-335 ekspresyon düzeyleri değerlendirilerek tümörün agresivitesi ve hastada metastaz gelişebilme riski ile ilgili bilgi edinilebilir. Mevcut bulgular, diğer meme kanserli hastalar ile benzer tedavi yaklaşımları uygulanarak takip edilen bu hasta grubunda, farklı etkin tedavi yaklaşımlarının düzenlenlenmesine katkı oluşturarak hastaların yaşam süresinin ve kalitesinin geliştirilmesine imkan sağlayacaktır. Ayrıca elde edilen bulgular; BRCA mutasyonu taşıyan meme kanserli hastalarda, kötü prognozun takibini sağlayabilecek biyobelirteçlerin belirlenmesi konusunda uluslararası ve ulusal literatüre katkı sağlar niteliktedir.
Breast cancer is the type of cancer most frequently seen among women in the world. Recently understanding the functions of microRNAs and their roles in cancer progression has been providing expectations for understanding the molecular pathology of breast cancer and developing new molecular targeted therapies.Samples were analyzed for the presence and differential expression of 14 miRNAs (miR-21, miR-155, miR-145, let-7a, miR-10b, miR-125b, miR-221, miR-222, miR-205, miR-126, miR-206, miR-200c, miR-31 and miR-335) known to be related to diagnosis, prognosis and drug resistance of breast cancer. Expression profiles of these miRNAs were evaluated for 60 familial and/or early-onset breast tumor and 20 non-tumor tissues of patients. In order to analysis of the data in the study Independent Samples t Test, Kaplan Meier Analysis, Linear Regression Analysis, Pearson Chi-square and Fishers Exact Test were performed. According to these analysis, let-7a and miR-335 were significantly down-regulated in patients with BRCA mutations in early-onset and/or or familial breast cancer cases. In the same time, these decrease evaluated association with tumor growth and metastasis. It was found significant as statistically (p=0.044, p=0.022).These data will be beneficial for evaluation of let-7a and miR-335 expression levels to obtain information about aggressiveness of tumor and metastasis risk in early onset and/or familial breast cancer patients with BRCA mutation. In addition, these results will contribute similar therapy approaches in other breast cancer patients, thus, patients survival rates and quality of their life may be improved. Moreover, our findings will be useful for the determination of biomarkers on the follow-up of poor prognosis in breast cancer patients with BRCA mutation that could contribute to the international and national literature.
Breast cancer is the type of cancer most frequently seen among women in the world. Recently understanding the functions of microRNAs and their roles in cancer progression has been providing expectations for understanding the molecular pathology of breast cancer and developing new molecular targeted therapies.Samples were analyzed for the presence and differential expression of 14 miRNAs (miR-21, miR-155, miR-145, let-7a, miR-10b, miR-125b, miR-221, miR-222, miR-205, miR-126, miR-206, miR-200c, miR-31 and miR-335) known to be related to diagnosis, prognosis and drug resistance of breast cancer. Expression profiles of these miRNAs were evaluated for 60 familial and/or early-onset breast tumor and 20 non-tumor tissues of patients. In order to analysis of the data in the study Independent Samples t Test, Kaplan Meier Analysis, Linear Regression Analysis, Pearson Chi-square and Fishers Exact Test were performed. According to these analysis, let-7a and miR-335 were significantly down-regulated in patients with BRCA mutations in early-onset and/or or familial breast cancer cases. In the same time, these decrease evaluated association with tumor growth and metastasis. It was found significant as statistically (p=0.044, p=0.022).These data will be beneficial for evaluation of let-7a and miR-335 expression levels to obtain information about aggressiveness of tumor and metastasis risk in early onset and/or familial breast cancer patients with BRCA mutation. In addition, these results will contribute similar therapy approaches in other breast cancer patients, thus, patients survival rates and quality of their life may be improved. Moreover, our findings will be useful for the determination of biomarkers on the follow-up of poor prognosis in breast cancer patients with BRCA mutation that could contribute to the international and national literature.
Description
Keywords
Meme kanseri, MikroRNA ekspresyonu, BRCA1/2 gen mutasyonları, RT-PCR, Breast cancer, MicroRNA expression, BRCA1/2 gene mutations, RTPCR
Citation
Ertürk, E. (2012). Meme kanseri gelişiminde miRNA' ların rolünün araştırılması. Yayınlanmamış yüksek lisans tezi. Uludağ Üniversitesi Sağlık Bilimleri Enstitüsü.