Publication: Meme kanserinde Hippo sinyal yolağı üzerinde yer alan NOS1AP'ın Epitelyal-Mezenkimal Geçiş (EMT) süreci ile arasındaki ilişkinin değerlendirilmesi
Abstract
1. ÖZET Tez Başlığı: Meme Kanserinde Hippo Sinyal Yolağı Uzerinde Yer Alan NOS1AP’ın Epitelyal-Mezenkimal Geciş (EMT) Sureci ile Arasındaki İlişkinin Değerlendirilmesi Oğrencinin Adı: Buşra POLAT Danışman: Prof. Dr. Mustafa AKKİPRİK Tıbbi Biyoloji ve Genetik Amac: Meme kanserinde, NOS1AP’nin Hippo sinyal yolağı ve EMT ile arasındaki ilişkinin aydınlatılması amaclandı. Gerec ve Yontem: 67 meme kanseri hastasının eşleştirilmiş sağlıklı ve primer kanser dokularında (13 bazal, 15 HER2, 20 luminal A ve 19 luminal B alt tiplerde) NOS1AP, YAP1, TAZ, TEAD2, SCRİBBLE, CTGF, PAI1, CDH1, TWIST1 ve VIMENTIN genlerinin ekspresyon seviyeleri qRT- PCR ile incelendi. Bulgular: Sağlıklı dokulara kıyasla meme kanseri dokularında TWIST1, VIMENTİN, YAP1 ve TAZ ekspresyonunun duşuk (p<0,05), CDH1 ekspresyonunun yuksek (p<0,05) olduğu tespit edildi. Luminal B alt tipinde NOS1AP ve CDH1 ekspresyonunun yuksek (p<0,05) ve HER2 alt tipinde ise NOS1AP ekspresyonunun sağlıklı dokulara gore duşuk (p<0,05) olduğu gozlendi. Ayrıca NOS1AP’nin sağlıklı dokularda ve belirli tumor alt tiplerinde Hippo yolağı uyeleri ve CDH1 ile pozitif korelasyon gosterdiği tespit edildi. Sonuc: Ekspresyon verileri, NOS1AP’nin HER2 alt tipinde tumor baskılayıcı, NOS1AP ve CDH1’in luminal B alt tipinde onkogen rolunun olabileceğine işaret eder. Bu, NOS1AP ve CDH1’in alt tipe ozel aday biyobelirtec olabileceğini duşundurur. Duşuk TWIST1, VIMENTİN ve yuksek CDH1 ekspresyon seviyesi primer meme kanseri dokularında epitelyal karakterin baskın olduğunu ve EMT’nin başlamadığını gosterdi. Bu nedenle NOS1AP ve EMT arasında bir ilişki saptanamadı. Ayrıca, Hippo bileşenleri YAP1 ve TAZ’nin duşuk ekspresyon seviyeleri de bu dokularda EMT’nin başlamadığına yonelik değerlendirmemizi destekledi. Korelasyon bulgularımız da meme kanserinde de NOS1AP ve Hippo yolağı uyeleri arasında bir ilişki olduğunu desteklemektedir.
2. SUMMARY Title of Thesis: Evaluation of the relationship between NOS1AP on the Hippo signaling pathway and the epithelial-mesenchymal transition (EMT) process in breast cancer Student Name, Surname: Buşra POLAT Supervisor Name: Prof. Dr. Mustafa AKKİPRİK Program Name: Tıbbi Biyoloji ve Genetik Objective: The aim of this study was to elucidate the relationship of NOS1AP between Hippo signaling pathway and EMT process in breast cancer. Material and Methods: Expression levels of NOS1AP, YAP1, TAZ, TEAD2, SCRİBBLE, CTGF, PAI1, CDH1, TWIST1 and VIMENTIN genes in matched healthy and primary cancer tissues of 67 breast cancer patients were examined by qRTPCR. Results: TWIST1, VIMENTIN, YAP1 and TAZ expression were lower (p<0.05) but CDH1 expression was higher in tumor tissues compared to healthy tissues (p<0.05). NOS1AP and CDH1 expressions were higher in luminal B subtype (p<0.05) and NOS1AP expression was lower in HER2 subtype (p<0.05) compared to healthy tissues. In addition, NOS1AP was positively correlated with Hippo pathway related genes and CDH1 in healthy tissues and certain tumor subtypes. Conclusion: Expression data indicate that NOS1AP may have a tumor suppressor role in the HER2 subtype and NOS1AP, CDH1 may have an oncogenic role in the luminal B subtype. This suggest that NOS1AP and CDH1 may be subtype-specific candidate biomarkers. Low TWIST1 and VIMENTIN expression and high CDH1 expression showed that epithelial character was predominant and EMT had not yet started in primary breast cancer tissues. Therefore, no association was found between NOS1AP and EMT. In addition, the low expression of the Hippo components YAP1 and TAZ supported our assessment that EMT was not initiated in cancer tissues. Our correlation findings also support a relationship between NOS1AP and Hippo pathway members in breast cancer.
2. SUMMARY Title of Thesis: Evaluation of the relationship between NOS1AP on the Hippo signaling pathway and the epithelial-mesenchymal transition (EMT) process in breast cancer Student Name, Surname: Buşra POLAT Supervisor Name: Prof. Dr. Mustafa AKKİPRİK Program Name: Tıbbi Biyoloji ve Genetik Objective: The aim of this study was to elucidate the relationship of NOS1AP between Hippo signaling pathway and EMT process in breast cancer. Material and Methods: Expression levels of NOS1AP, YAP1, TAZ, TEAD2, SCRİBBLE, CTGF, PAI1, CDH1, TWIST1 and VIMENTIN genes in matched healthy and primary cancer tissues of 67 breast cancer patients were examined by qRTPCR. Results: TWIST1, VIMENTIN, YAP1 and TAZ expression were lower (p<0.05) but CDH1 expression was higher in tumor tissues compared to healthy tissues (p<0.05). NOS1AP and CDH1 expressions were higher in luminal B subtype (p<0.05) and NOS1AP expression was lower in HER2 subtype (p<0.05) compared to healthy tissues. In addition, NOS1AP was positively correlated with Hippo pathway related genes and CDH1 in healthy tissues and certain tumor subtypes. Conclusion: Expression data indicate that NOS1AP may have a tumor suppressor role in the HER2 subtype and NOS1AP, CDH1 may have an oncogenic role in the luminal B subtype. This suggest that NOS1AP and CDH1 may be subtype-specific candidate biomarkers. Low TWIST1 and VIMENTIN expression and high CDH1 expression showed that epithelial character was predominant and EMT had not yet started in primary breast cancer tissues. Therefore, no association was found between NOS1AP and EMT. In addition, the low expression of the Hippo components YAP1 and TAZ supported our assessment that EMT was not initiated in cancer tissues. Our correlation findings also support a relationship between NOS1AP and Hippo pathway members in breast cancer.