Moleküler parametreler ile metastatik karaciğer kanserlerinde metastazektomi sonrasi nüksün öngörülmesi mümkün mü? retrospektif çalişma
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Date
2021
Authors
Karamustafaoğu, Ahmet
Journal Title
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Volume Title
Publisher
Bursa Uludağ Üniversitesi
Abstract
Planlanan bu tez çalışmasında, kolorektal tümörlerden köken alan metastatik karaciğer kanserlerinde (mKK) takip sırasında oluşan nükse ve kısa sağkalıma neden olan genetik ve epigenetik sinyal yolaklarının araştırılarak rutin pratikte kullanılabilecek güçlü bir biyobelirtecin tanımlanması amaçlanmaktadır. Mevcut tez çalışmasında hasta seçim kriterleri doğrultusunda belirlenen mKK'larda ve primer kolorektal kanserlerde, gerçek zamanlı PCR kullanılarak kök hücre belirteçleri, RAS, PIK3CA, P53, mTOR, VEGF sinyal yolaklarının ve EMT mekanizmasının aktivitesi incelendi. Web tabanlı Sabiosciences PCR-Data Analiz programından yararlanılarak, gruplar arasında mRNA ekspresyon düzeyindeki değişimleri ifade eden kat değişimleri belirlendi. Çalışmada 85 primer kolorektal kanser vakası değerlendirildi. 21 vakada (%24.7) mKK gelişimi gözlendi. Metastazektomi sonrası 21 vakanın 9'unda nüks belirlendi. Genel sağ kalım ortalama 84 ay olarak belirlendi. Hastalıksız sağ kalım da ortalama 51 ay olarak saptandı. Kök hücre CD44, EMT'den SNAIL, TWIST, MEK ve mTOR ekspresyonlarının mKK gelişiminde etkili olduğu saptandı. CD44, mTOR ve SNAIL yüksek ekspresyonları metastazektomi sonrası nüks gelişiminde etkili olduğu gösterildi. Bu çalışmada, CD44, mTOR ve SNAIL'in primer kolorektal tümörlerde yüksek ekspresyonlarının ileride gelişecek mKK ve hatta mKK'larda metastazektomi sonrasında gelişecek nüksü öngörmede kullanılabilecek biyobelirteç adayları olduğu belirlendi. Anahtar Kelimler: Karaciğer metastazları, metastazektomi, sinyal yolakları, RT-PCR, kolorektal kanser
In this planned thesis study, it is aimed to define a strong biomarker that can be used in routine practice by investigating the genetic and epigenetic signaling pathways that cause recurrence and short survival during follow-up in metastatic liver cancers (mCC) originating from colorectal tumors. In the current thesis study, the activity of stem cell markers, RAS, PIK3CA, P53, mTOR, VEGF signaling pathways and EMT mechanism were investigated using real-time PCR in mCCs and primary colorectal cancers determined in accordance with patient selection criteria. Using the web-based Sabiosciences PCR-Data Analysis program, fold changes expressing changes in mRNA expression level between groups were determined. In the study, 85 primary colorectal cancer cases were evaluated. CCT development was observed in 21 cases (24.7%). After metastasectomy, recurrence was detected in 9 of 21 cases. The mean overall survival was determined as 84 months. Disease-free survival was also found to be 51 months on average. Stem cell CD44, SNAIL, TWIST, MEK and mTOR expressions from EMT were found to be effective in the development of mKK. High expressions of CD44, mTOR and SNAIL were shown to be effective in the development of recurrence after metastasectomy. In this study, it was determined that the high expressions of CD44, mTOR and SNAIL in primary colorectal tumors are biomarker candidates that can be used to predict future mCC and even recurrence after metastasectomy in mCCs. Key Words: Liver metastasis, metastasectomy, siganling pathways, RT-PCR, colorectal cancer
In this planned thesis study, it is aimed to define a strong biomarker that can be used in routine practice by investigating the genetic and epigenetic signaling pathways that cause recurrence and short survival during follow-up in metastatic liver cancers (mCC) originating from colorectal tumors. In the current thesis study, the activity of stem cell markers, RAS, PIK3CA, P53, mTOR, VEGF signaling pathways and EMT mechanism were investigated using real-time PCR in mCCs and primary colorectal cancers determined in accordance with patient selection criteria. Using the web-based Sabiosciences PCR-Data Analysis program, fold changes expressing changes in mRNA expression level between groups were determined. In the study, 85 primary colorectal cancer cases were evaluated. CCT development was observed in 21 cases (24.7%). After metastasectomy, recurrence was detected in 9 of 21 cases. The mean overall survival was determined as 84 months. Disease-free survival was also found to be 51 months on average. Stem cell CD44, SNAIL, TWIST, MEK and mTOR expressions from EMT were found to be effective in the development of mKK. High expressions of CD44, mTOR and SNAIL were shown to be effective in the development of recurrence after metastasectomy. In this study, it was determined that the high expressions of CD44, mTOR and SNAIL in primary colorectal tumors are biomarker candidates that can be used to predict future mCC and even recurrence after metastasectomy in mCCs. Key Words: Liver metastasis, metastasectomy, siganling pathways, RT-PCR, colorectal cancer
Description
Keywords
Karaciğer metastazları, Metastazektomi, Sinyal yolakları, RT-PCR, Kolorektal kanser, Liver metastasis, Metastasectomy, Signaling pathways, Colorectal cancer
Citation
Karamustafaoğlu, A. (2021). Moleküler parametreler ile metastatik karaciğer kanserlerinde metastazektomi sonrasi nüksün öngörülmesi mümkün mü? retrospektif çalişma. Yayınlanmamış tıpta uzmanlık tezi. Bursa Uludağ Üniversitesi Tıp Fakültesi.