Rahim Ağzı Kanser Alt-Tiplerine Özgü Moleküler Hedef, Biyoişaretçi Adaylar ve Yeniden Konumlandırılan İlaçların Belirlenmesi

Beste Turanlı

doi:10.7240/jeps.869943

Rahim Ağzı Kanser Alt-Tiplerine Özgü Moleküler Hedef, Biyoişaretçi Adaylar ve Yeniden Konumlandırılan İlaçların Belirlenmesi

Abstract

Hassas tıp uygulamaları, geleneksel tedaviden farklı olarak kanser hastaları arasındaki bireysel farklılıkları dikkate alarak hastaları sınıflandırır. Yapılan alt tipleme ile kanser teşhisi ve tedavi yanıtının tahmini için yeni biyobelirteçlerin belirlenmesi gerekmektedir. Bu çalışmada, sistem biyolojisi yaklaşımları kullanılarak, rahim ağzı kanserinin en yaygın onkojenik iki türü olan HPV-16 enfekte ve HPV-18 enfekte grupları ayrı ayrı incelenmiştir. Her iki alt-tip için kanserin gelişimi ile ilgili ayırıcı biyobelirteçler sunularak, hassas tıp uygulaması olabilecek alt-tip spesifik teşhis ve tedavi yöntemleri sunma konusunda moleküler hedefler sunulması amaçlanmıştır. Literatürde var olan çalışmalar, hastalık heterojenliği ve alt-tip bilgilerinden bağımsız olarak doğrudan rahim ağzı kanserine odaklanmıştır. İlk defa bu çalışmada HPV-16 ve HPV-18 enfekte hasta grupları ile ilgili transkriptomik veri ayrı ayrı çalışılmıştır. Rahim ağzı kanserinde alt-tip spesifik diyagnostik, prognostik ve ilaç hedefi olabilecek biyobelirteçlerini belirlemek için mikrodizi meta-analizi yapılmıştır. İlk olarak incelenen protein-protein etkileşimlerindeki hub proteinlerde iki alt-tipte de ortak olan 8 protein (AR, AURKA, BRCA1, CDKN2A, EZH2, MYC, PCNA, STAT) dışında, 17’şer protein alt-tiplere spesifik hub proteinler olarak bulunmuştur. Transkripsiyonel düzenlemede önem arz eden TF ve miRNA’lar arasında işaretçi molekül algoritması ile ön plana çıkanlar bulunmuştur. TF’lerde alt-tipleri ayırt edebilecek belirgin farklılık gözlenmemekle birlikte, sadece HIF1α HPV-18 enfekte grubunda işaretçi TF bulunmuştur. HPV-16 spesifik sadece hsa-miR-101-3p ve hsa-let-7d-5p bulunmuştur. HPV-18 enfekte gruba spesifik ise 81 miRNA vardır. Çalışmanın en sonunda ise hub proteinlerin bazılarını hedef alan ilaçlar üzerinden ilaç yeniden konumlandırma yapılmıştır. HPV-16 enfekte kanser tedavisi için ibuprofen ve procainamide ilaçları; HPV-18 enfekte kanserler için ise hydralazine ve memantin önerilen ilaçlardandır.

Keywords

Supporting Institution

TÜBİTAK

Project Number

119S999

Thanks

Bu çalışma, 119S999 numaralı TÜBİTAK 1002 Araştırma projesi kapsamında desteklenmiştir.

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Details

Primary Language

Turkish

Subjects

Engineering

Journal Section

Research Article

Authors

Beste Turanlı ^*
0000-0003-1330-9712
Türkiye

Publication Date

December 30, 2021

Submission Date

January 28, 2021

Acceptance Date

March 26, 2021

Published in Issue

Year 2021 Volume: 33 Number: 4

DOI

https://doi.org/10.7240/jeps.869943

IZ

https://izlik.org/JA56DL92LX

Cite

RIS / Bibtex

APA

Turanlı, B. (2021). Rahim Ağzı Kanser Alt-Tiplerine Özgü Moleküler Hedef, Biyoişaretçi Adaylar ve Yeniden Konumlandırılan İlaçların Belirlenmesi. International Journal of Advances in Engineering and Pure Sciences, 33(4), 537-548. https://doi.org/10.7240/jeps.869943

AMA

1.Turanlı B. Rahim Ağzı Kanser Alt-Tiplerine Özgü Moleküler Hedef, Biyoişaretçi Adaylar ve Yeniden Konumlandırılan İlaçların Belirlenmesi. JEPS. 2021;33(4):537-548. doi:10.7240/jeps.869943

Chicago

Turanlı, Beste. 2021. “Rahim Ağzı Kanser Alt-Tiplerine Özgü Moleküler Hedef, Biyoişaretçi Adaylar Ve Yeniden Konumlandırılan İlaçların Belirlenmesi”. International Journal of Advances in Engineering and Pure Sciences 33 (4): 537-48. https://doi.org/10.7240/jeps.869943.

EndNote

Turanlı B (December 1, 2021) Rahim Ağzı Kanser Alt-Tiplerine Özgü Moleküler Hedef, Biyoişaretçi Adaylar ve Yeniden Konumlandırılan İlaçların Belirlenmesi. International Journal of Advances in Engineering and Pure Sciences 33 4 537–548.

IEEE

[1]B. Turanlı, “Rahim Ağzı Kanser Alt-Tiplerine Özgü Moleküler Hedef, Biyoişaretçi Adaylar ve Yeniden Konumlandırılan İlaçların Belirlenmesi”, JEPS, vol. 33, no. 4, pp. 537–548, Dec. 2021, doi: 10.7240/jeps.869943.

ISNAD

Turanlı, Beste. “Rahim Ağzı Kanser Alt-Tiplerine Özgü Moleküler Hedef, Biyoişaretçi Adaylar Ve Yeniden Konumlandırılan İlaçların Belirlenmesi”. International Journal of Advances in Engineering and Pure Sciences 33/4 (December 1, 2021): 537-548. https://doi.org/10.7240/jeps.869943.

JAMA

1.Turanlı B. Rahim Ağzı Kanser Alt-Tiplerine Özgü Moleküler Hedef, Biyoişaretçi Adaylar ve Yeniden Konumlandırılan İlaçların Belirlenmesi. JEPS. 2021;33:537–548.

MLA

Turanlı, Beste. “Rahim Ağzı Kanser Alt-Tiplerine Özgü Moleküler Hedef, Biyoişaretçi Adaylar Ve Yeniden Konumlandırılan İlaçların Belirlenmesi”. International Journal of Advances in Engineering and Pure Sciences, vol. 33, no. 4, Dec. 2021, pp. 537-48, doi:10.7240/jeps.869943.

Vancouver

1.Beste Turanlı. Rahim Ağzı Kanser Alt-Tiplerine Özgü Moleküler Hedef, Biyoişaretçi Adaylar ve Yeniden Konumlandırılan İlaçların Belirlenmesi. JEPS. 2021 Dec. 1;33(4):537-48. doi:10.7240/jeps.869943