Kodlama yapmayan uzun RNA'ların kolon tümörlerinde prognoz açısından öneminin araştırılması
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Date
2019-09-13
Authors
Aksoy, Seçil
Journal Title
Journal ISSN
Volume Title
Publisher
Bursa Uludağ Üniversitesi
Abstract
Kodlama Yapmayan Uzun RNA' ların Kolon Tümörlerinde Prognoz Açısından Öneminin Araştırılması Erken evre kolon kanserlerinde (KK) tedavi protokollerini belirlemede ve nüksü öngörmede mevcut parametreler yetersiz kalmaktadır. Ayrıca kötü prognostik faktörleri olmayan ancak nüks potansiyeli belirlenen erken evre KK'ların standart tedavilere verecekleri yanıt da bilinmemektedir. Mevcut tez çalışmasında kötü prognostik faktörleri bulunmayan erken evre KK'larda prognozu belirlemede kullanılabilecek parametrelerin tanımlanması ve belirlenmesi öngörülen parametrelerden yararlanılarak adjuvan tedavi planlanacak tümörlerde, ilaç direnç durumunun değerlendirilmesi amaçlanmıştır. Mevcut tez çalışmasında, 2005-2013 yılları arasında erken evre (T1-3N0M0), herhangi bir kötü prognostik faktörü bulunmayan, KK tanısı alan 126 hasta değerlendirildi. Nüks potansiyeli belirlenen hastaların tedaviye verecekleri yanıtı öngörmek için 5FU'ya dirençli HT29FUR hücreleri oluşturularak, bu hücrelerin metastatik özellikleri ve tümör dokularda incelenen parametreler değerlendirildi. İlaç direnç gelişimi ve metastaz arasındaki olası sinerji, fonksiyonel analizler (yara iyileştirmesi ve koloni oluşumu) ile incelendi. 126 hastanın takip sırasında 21'inde nüks gelişimi belirlendi. MACC1'in ve MALAT1'in yüksek, PTENP1'in ve NM23-H1'in ise düşük ekspresyonları ve tümör tomurcuklanması varlığı, erken evre KK tümörlerinin nüks gelişimi ile ilişkili olarak belirledi (p<0.05). İlaç direncini öngörmek için oluşturulan HT-29FUR hücrelerinde de MALAT1'in yüksek, PTENP1'in düşük ekspresyonu tanımlandı. Bununla birlikte fonksiyonel analizler ile ilaç direnci oluşumu sırasında hücrelerin metastaz yetenekleri de kazandıkları kanıtlandı. Sonuç olarak, MALAT1 ve PTENP1'in erken evre KK'larda nüks potansiyelini belirlemede ideal birer biyobelirteç adayı oldukları ve bu tip tümörlerde yeni tedavi stratejilerinin geliştirilmesinde bu LncRNA'ların hücre içinde hedeflenerek tedavi sürecine katkı sağlayabileceklerinin mümkün olabileceği belirlendi.
In early stage colon cancer (CC), current parameters are insufficient to determine the treatment protocols and to predict recurrence. In addition, the response to early treatment of early stage CBCs with poor prognostic factors but with a potential for recurrence is unknown. In the present study, it was aimed to define the parameters that can be used to determine the prognosis in early stage CCI without bad prognostic factors and to evaluate the drug resistance status in tumors that will be planned adjuvant treatment by using the parameters that are intended to be determined. In the present study, 126 patients with early stage (T1-3N0M0) who did not have any poor prognostic factors were evaluated. 5FU-resistant HT29FUR cells were formed to predict the response of patients to whom recurrence potential was determined and the metastatic characteristics of these cells and the parameters examined in tumor tissues were evaluated. The possible synergy between drug resistance development and metastasis was examined by functional analysis (wound healing and colony formation). Recurrence was detected in 21 of 126 patients during follow-up. The presence of high expression of MACC1 and MALAT1, low expression of PTENP1 and NM23-H1 and tumor budding were found to be associated with the recurrence of early stage tumors (p <0.05). High expression of MALAT1 and low expression of PTENP1 were determined in HT-29FUR cells which were established to predict drug resistance. However, functional analysis showed that the cells gained metastasis ability during drug resistance formation. As a result, it was determined that MALAT1 and PTENP1 are ideal biomarker candidates to determine the recurrence potential in early stage CC and these LncRNAs will be targeted in the cell and contribute to the treatment process in the development of new treatment strategies for such tumors.
In early stage colon cancer (CC), current parameters are insufficient to determine the treatment protocols and to predict recurrence. In addition, the response to early treatment of early stage CBCs with poor prognostic factors but with a potential for recurrence is unknown. In the present study, it was aimed to define the parameters that can be used to determine the prognosis in early stage CCI without bad prognostic factors and to evaluate the drug resistance status in tumors that will be planned adjuvant treatment by using the parameters that are intended to be determined. In the present study, 126 patients with early stage (T1-3N0M0) who did not have any poor prognostic factors were evaluated. 5FU-resistant HT29FUR cells were formed to predict the response of patients to whom recurrence potential was determined and the metastatic characteristics of these cells and the parameters examined in tumor tissues were evaluated. The possible synergy between drug resistance development and metastasis was examined by functional analysis (wound healing and colony formation). Recurrence was detected in 21 of 126 patients during follow-up. The presence of high expression of MACC1 and MALAT1, low expression of PTENP1 and NM23-H1 and tumor budding were found to be associated with the recurrence of early stage tumors (p <0.05). High expression of MALAT1 and low expression of PTENP1 were determined in HT-29FUR cells which were established to predict drug resistance. However, functional analysis showed that the cells gained metastasis ability during drug resistance formation. As a result, it was determined that MALAT1 and PTENP1 are ideal biomarker candidates to determine the recurrence potential in early stage CC and these LncRNAs will be targeted in the cell and contribute to the treatment process in the development of new treatment strategies for such tumors.
Description
Keywords
Erken evre, Kolon kanseri, Kodlama yapmayan uzun RNA’lar, İlaç dirençliliği, Epitelyal-mezenkimal geçiş, Early stage, Colon cancer, Long non-coding RNA, Drug resistance, Epithelial mesenchymal transition
Citation
Aksoy, S. (2019). Kodlama yapmayan uzun RNA'ların kolon tümörlerinde prognoz açısından öneminin araştırılması. Yayınlanmamış doktora tezi. Bursa Uludağ Üniversitesi Sağlık Bilimleri Enstitüsü.