Meme kanserinde HOXB13 VE IL17BR genlerinin ve bu genler ile ilişkili miRNA'ların prognostik ve prediktif önemi
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Date
2013
Authors
Demirdöğen, Elif
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Publisher
Uludağ Üniversitesi
Abstract
Meme kanseri, dünyada kadınlar arasında en sık görülen kanser türüdür. Son yıllarda meme kanseri oluşumunda rol oynayan genlerin ve mikroRNA (miRNA)'ların işlevlerinin anlaşılmaya başlanması, hem meme kanserinin moleküler patolojisinin anlaşılmasını hem de yeni moleküler hedefe yönelik tedavilerin geliştirilmesini sağlamaktadır. Çalışmada, ER(+) Türk primer meme kanserli 40 hastanın tümör, normal doku ve periferik kan örneklerinde; meme kanseri gelişiminde prognostik ve prediktif açıdan önemli olan HOXB13 ve IL17BR genlerinin ve bu genleri hedef alan miRNA' ların (miR-661, miR-1260, miR-1278 ve miR-1266) ekspresyon analizleri gerçekleştirilmiştir. Elde edilen veriler; Bağımsız İki Örnek t-testi, İşlem Karakteristik Eğrisi, Lojistik Regresyon, Kaplan Maier ve Cox Oransal Risk Regresyon Analizi ile değerlendirilmiştir. Hastaların tümör dokularında normal dokuya göre, HOXB13 ekspresyon seviyesinde 1.31 kat artış, IL17BR ekspresyon seviyesinde ise 0.80 kat azalış belirlenmesine rağmen istatistiki bir anlamlılık saptanmamıştır (p= 0.3559, p= 0.3166). HOXB13:IL17BR ekspresyon oranındaki artışın sağkalım ve tedaviye yanıt ile ilişkisi anlamlı bulunmuştur (p= 0.0491, p= 0.0267). miR-661, miR-1260, miR-1266 ekspresyon seviyeleri, tümör dokuda normal dokuya göre sırasıyla; 1.94, 1.59 ve 1.38 kat artış; miR-1278 ekspresyon seviyesi ise 0.30 kat azalış göstermiştir (p= 0.3578, p= 0.3451, p= 0.6930, p= 0.2428). Rekürens/metastaz (-) hastalar ile rekürens/metastaz(+) hastalar arasında HOXB13'ü hedef alan miR-1278 ve IL17BR'yi hedef alan miR-1266 ekspresyon seviyelerinde istatistiksel olarak anlamlı farklılık gözlenmiştir (p = 0.0014, p= 0.0048). Hastaların periferik kanlarında ise HOXB13 ve IL17BR genlerinin ekspresyonu gözlenmemiştir. Elde edilen bulgular ışığında; ER(+) primer meme tümörlerinde HOXB13 ve IL17BR'yi hedefleyen miRNA düzeylerindeki farklılıklar değerlendirilerek, tümörün agresivitesi ve metastaz riski hakkında bilgi edinilebilecektir. Böylece, farklı etkin tedavi yaklaşımlarının düzenlenmesi ve hastaların yaşam süresi ve kalitesinin geliştirilebilmesine yönelik çalışmalara katkı sağlanabilecektir. Ayrıca mevcut çalışma; ER(+) Türk primer meme kanserli hastalarda, kötü prognozun takibinde ve uygulanan tedavinin etkinliğinde faydalanılabilecek miRNA düzeyindeki biyobelirteçlerin belirlenmesi konusunda yapılacak ileri çalışmalara yol gösterici olan, uluslararası ve ulusal literatüre katkı sağlayabilecek nitelikteki ilk çalışmadır.
Breast cancer is the most common type of cancer among women worldwide. In recent years, understanding the functions of genes and miRNAs that play a role in breast cancer development, has been providing expectations for understanding the molecular pathology of breast cancer as well as developing new molecular targeted therapies. In this study, the expression analysis of HOXB13 and IL17BR genes and their target miRNAs (miR-661, miR-1260, miR-1278 ve miR-1266) carried out in tumor, normal tissue and peripheral blood samples of 40 ER(+) Turkish primary breast cancer patients. Obtained data were evaluated by Independent Samples t-test, ROC Curve, Logistic Regression, Kaplan Maier and Cox Proportional Hazards Regression Analysis. Expression levels of HOXB13 is 1.31 fold higher and expression levels of IL17BR is 0.80 fold lower in tumor samples than normal tissues of patients but it isn't determined any statistical significance (p = 0.3559, p = 0.3166). An increase in HOXB13:IL17BR gene expression ratio is significantly correlated with survival of breast cancer patients and treatment response (p= 0.0491, p= 0.0267). miR-661, miR-1260 and miR-1266 expression levels are 1.94, 1.59 and 1.38 fold higher and miR-1278 expression level is 0,30 fold lower in tumor than normal tissue (p= 0.3578, p= 0.3451, p= 0.6930, p= 0.2428). HOXB13 associated miR-1278 and IL17BR associated miR-1266 expression levels are significantly correlated with recurrence/distant metastasis (p = 0.0014, p = 0.0048). HOXB13 and IL17BR gene expressions are not observed in peripheral blood samples of patients. These data will be beneficial for evaluation of miRNA expression levels target HOXB13 and IL17BR to obtain information about tumor aggressiveness and metastasis risk in ER(+) primary breast cancer patients. In this manner, it can be contributed to the studies of organization of different effective treatment approaches and improvement the quality of life and survival of patients. Moreover, the present study is the first study that can contribute to the international and national literature in terms of guide for further studies for the determination of biomarkers in miRNA levels providing follow-up of poor prognosis and evaluating the effectiveness of the treatment in ER(+) Turkish primary breast cancer patients.
Breast cancer is the most common type of cancer among women worldwide. In recent years, understanding the functions of genes and miRNAs that play a role in breast cancer development, has been providing expectations for understanding the molecular pathology of breast cancer as well as developing new molecular targeted therapies. In this study, the expression analysis of HOXB13 and IL17BR genes and their target miRNAs (miR-661, miR-1260, miR-1278 ve miR-1266) carried out in tumor, normal tissue and peripheral blood samples of 40 ER(+) Turkish primary breast cancer patients. Obtained data were evaluated by Independent Samples t-test, ROC Curve, Logistic Regression, Kaplan Maier and Cox Proportional Hazards Regression Analysis. Expression levels of HOXB13 is 1.31 fold higher and expression levels of IL17BR is 0.80 fold lower in tumor samples than normal tissues of patients but it isn't determined any statistical significance (p = 0.3559, p = 0.3166). An increase in HOXB13:IL17BR gene expression ratio is significantly correlated with survival of breast cancer patients and treatment response (p= 0.0491, p= 0.0267). miR-661, miR-1260 and miR-1266 expression levels are 1.94, 1.59 and 1.38 fold higher and miR-1278 expression level is 0,30 fold lower in tumor than normal tissue (p= 0.3578, p= 0.3451, p= 0.6930, p= 0.2428). HOXB13 associated miR-1278 and IL17BR associated miR-1266 expression levels are significantly correlated with recurrence/distant metastasis (p = 0.0014, p = 0.0048). HOXB13 and IL17BR gene expressions are not observed in peripheral blood samples of patients. These data will be beneficial for evaluation of miRNA expression levels target HOXB13 and IL17BR to obtain information about tumor aggressiveness and metastasis risk in ER(+) primary breast cancer patients. In this manner, it can be contributed to the studies of organization of different effective treatment approaches and improvement the quality of life and survival of patients. Moreover, the present study is the first study that can contribute to the international and national literature in terms of guide for further studies for the determination of biomarkers in miRNA levels providing follow-up of poor prognosis and evaluating the effectiveness of the treatment in ER(+) Turkish primary breast cancer patients.
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Keywords
Meme kanseri, ER, HOXB13, IL17BR, MikroRNA, Breast cancer, MicroRNA
Citation
Demirdöğen, D. (2013). Meme kanserinde HOXB13 VE IL17BR genlerinin ve bu genler ile ilişkili miRNA'ların prognostik ve prediktif önemi. Yayınlanmamış yüksek lisans tezi. Uludağ Üniversitesi Fen Bilimleri Enstitüsü.