Retrospective analysis of yap/TAZ/ MST/lats gene expressions in ınvasive ductal carcinoma breast cancer patients
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Date
2019-08-19
Authors
Takanlou, Maryam Sabour
Journal Title
Journal ISSN
Volume Title
Publisher
Bursa Uludağ Üniversitesi
Abstract
Meme kanseri kadınlarda en sık görülen kanserdir. Ülkemizde meme kanseri görülme sıklığındaki artış ve görülme yaşındaki düşüş göz önüne alındığında meme kanseri farkındalığı ve tarama programlarının önemi gün geçtikçe daha da artmaktadır. Ayrıca, meme kanseri tedavileri, direnç ve güvenilir biyobelirteç eksikliği gibi birçok sınırlamaya sahiptir. Günümüzde yapılan araştırmalar, Hippo yolağının, hücre çoğalmasının ve apoptozun kontrolünde rol oynadığı gösterilmiş olup, bu yolakta görev yapan genlerde meydana gelen değişikliklerin kanser gelişimi ile ilişkili olduğu ifade edilmektedir. Bununla birlikte, meme kanseri gelişiminde Hippo yolağın düzensizliklerinin moleküler mekanizması ve Hippo yolağı bileşenlerinin klinikopatolojik özelliklerle ilişkisi henüz açıklanmamıştır. Bu çalışmada, invaziv duktal karsinom teşhisi almış meme kanseri hastalarında Hippo yolağında görevli YAP/ TAZ/ MST/ LATS genlerinin ekspresyonları retrospektif olarak RT-PCR yöntemi ile araştırıldı ve bu genlerin ifade düzeylerindeki değişiklikler hastaların klinikopatolojik özellikleri ile karşılaştırıldı. Elde edilen bulgular meme kanserli hastaların tümor dokularında YAP1, LATS1 ve LATS2 ifadelerinin istatistiksel olarak anlamlı oranda (p=0.000; p=0.0004; p=0.0001; sırasıyla) down-regüle edildiğini göstermiştir. Ayrıca, çalışmada Hippo yolağının önemli bileşeni YAP mRNA ekspresyonu ile PR, grade ve ki-67 indeksi, tümör çapı, metastaz ve lenf nodu arasında anlamlı ilişki olduğu belirlendi. LATS2 mRNA ifadesindeki farklılığın ise; ki-67, tümör metastazı ve lenf nodu ile istatistiksel olarak anlamlılık gösterdiği belirlendi. Sonuç olarak, Hippo yolağı ile ilgili literatürde yer alan deneysel araştırmalara mevcut tez çalışmasında elde edilen klinik verilerin katkısı ile Hippo yolağının meme kanseri gelişiminde önemli rolü olduğu gösterilmiştir.
Breast cancer is the most frequent cancer type in women. When we consider the increase in its the frequency and the decrease in age of diagnosed patients, we realize that the importance of a screening program and breast cancer awareness is increasing day by day in our country. Also, treatments for breast cancer have many limitations, such as resistance and a lack of reliable biomarkers. Recent studies have also shown that aberrant Hippo pathway functioning can drive tumor formation and breast cancer metastasis due to its critical role in regulating cellular proliferation and organ size. This signaling controls cancer development, cell proliferation, and regulation of apoptosis. However, the detailed molecular mechanism that regulates the Hippo signaling in breast cancer metastasis, and the association of Hippo pathway components levels with clinicopathological characteristics are yet to be fully elucidated. In the present study, the Hippo pathway member levels (YAP1, TAZ, LATS1/2, MST1/2) in 100 patients with IDC breast cancer analyzed, and the association of Hippo pathway components levels with survival and clinicopathological characteristics of patients by RT-PCR were assessed. Our study showed that YAP1, LATS1, and LATS2 were significantly (p= 0,000; p= 0,0004; p= 0,0001; respectively) down-regulated in tumor tissues. Also, in this study observed significant association between the expression of low-YAP with PR status, HER2 status, tumor grade, Ki-67 proliferation index, metastasis tumors, lymph node, and tumor size. As well as, in the present study demonstrated significant association between the expression of low-LATS2 with Ki-67 proliferation index, metastasis tumors, and lymph node. In conclusion, studies are shown that the Hippo pathway plays an important role in the development of breast cancer by combining the clinical data obtained from the experimental studies in the literature.
Breast cancer is the most frequent cancer type in women. When we consider the increase in its the frequency and the decrease in age of diagnosed patients, we realize that the importance of a screening program and breast cancer awareness is increasing day by day in our country. Also, treatments for breast cancer have many limitations, such as resistance and a lack of reliable biomarkers. Recent studies have also shown that aberrant Hippo pathway functioning can drive tumor formation and breast cancer metastasis due to its critical role in regulating cellular proliferation and organ size. This signaling controls cancer development, cell proliferation, and regulation of apoptosis. However, the detailed molecular mechanism that regulates the Hippo signaling in breast cancer metastasis, and the association of Hippo pathway components levels with clinicopathological characteristics are yet to be fully elucidated. In the present study, the Hippo pathway member levels (YAP1, TAZ, LATS1/2, MST1/2) in 100 patients with IDC breast cancer analyzed, and the association of Hippo pathway components levels with survival and clinicopathological characteristics of patients by RT-PCR were assessed. Our study showed that YAP1, LATS1, and LATS2 were significantly (p= 0,000; p= 0,0004; p= 0,0001; respectively) down-regulated in tumor tissues. Also, in this study observed significant association between the expression of low-YAP with PR status, HER2 status, tumor grade, Ki-67 proliferation index, metastasis tumors, lymph node, and tumor size. As well as, in the present study demonstrated significant association between the expression of low-LATS2 with Ki-67 proliferation index, metastasis tumors, and lymph node. In conclusion, studies are shown that the Hippo pathway plays an important role in the development of breast cancer by combining the clinical data obtained from the experimental studies in the literature.
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Keywords
YAP, TAZ, MST, LATS, Meme kanseri, Breast cancer
Citation
Takanlou, M.S. (2019). Retrospective analysis of yap/TAZ/ MST/lats gene expressions in invasive ductal carcinoma breast cancer patients. Yayınlanmamış yüksek lisans tezi. Bursa Uludağ Üniversitesi Sağlık Bilimleri Enstitüsü.