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

Year 2021, Volume: 33 Issue: 4, 537 - 548, 30.12.2021

Beste Turanlı

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

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

Sistem biyotıbbı rahim-ağzı kanseri biyobelirteçler hastalık alt-tipleri ilaç yeniden konumlandırma

Supporting Institution

TÜBİTAK

Project Number

119S999

Thanks

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

References

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Year 2021, Volume: 33 Issue: 4, 537 - 548, 30.12.2021

Beste Turanlı

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

Abstract

Project Number

119S999

References

  • [1] Bray, F. ve Ferlay, J. ve Soerjomataram, I. ve Siegel, R.L. ve Torre, L.A. ve Jemal, A. (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians.
  • [2] Siegel, R.L. ve Miller, K.D. ve Jemal, A. (2020) Cancer statistics, 2020. CA: A Cancer Journal for Clinicians.
  • [3] Kori, M. ve Arga, K.Y. (2018) Potential biomarkers and therapeutic targets in cervical cancer: Insights from the meta-analysis of transcriptomics data within network biomedicine perspective. PLoS ONE.
  • [4] Lin, M. ve Ye, M. ve Zhou, J. ve Wang, Z.P. ve Zhu, X. (2019) Recent Advances on the Molecular Mechanism of Cervical Carcinogenesis Based on Systems Biology Technologies. Computational and Structural Biotechnology Journal.
  • [5] Mousavi, S.Z. ve Poortahmasebi, V. ve Mokhtari-azad, T. ve Shahmahmoodi, S. (2020) CDK1 and PLK1 are key regulator proteins in human Papilloma virus Type 16- Positive Cervical Cancer: A Network-Based Study. Medical Science. 24(101) (January), 201–214.
  • [6] Turanli, B. ve Altay, O. ve Borén, J. ve Turkez, H. ve Nielsen, J. ve Uhlen, M. ve et al. (2019) Systems biology based drug repositioning for development of cancer therapy. Seminars in Cancer Biology.
  • [7] Banno, K. ve Iida, M. ve Yanokura, M. ve Irie, H. ve Masuda, K. ve Kobayashi, Y. ve et al. (2015) Drug repositioning for gynecologic tumors: a new therapeutic strategy for cancer. TheScientificWorldJournal.
  • [8] Sharma, S. ve Baksi, R. ve Agarwal, M. (2016) Repositioning of anti-viral drugs as therapy for cervical cancer. Pharmacological Reports. 68 (5), 983–989.
  • [9] Clough, E. ve Barrett, T. (2016) The Gene Expression Omnibus database. Methods in Molecular Biology. 1418 (301), 93–110.
  • [10] Parkinson, H. ve Kapushesky, M. ve Shojatalab, M. ve Abeygunawardena, N. ve Coulson, R. ve Farne, A. ve et al. (2007) ArrayExpress - A public database of microarray experiments and gene expression profiles. Nucleic Acids Research.
  • [11] Irizarry, R.A. ve Hobbs, B. ve Collin, F. ve Beazer-Barclay, Y.D. ve Antonellis, K.J. ve Scherf, U. ve et al. (2003) Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics (Oxford, England).
  • [12] Smyth, G.K. ve Ritchie, M. ve Thorne, N. (2010) Linear Models for Microarray Data User ’ s Guide.
  • [13] Pagès, H. ve Carlson, M. ve Falcon, S. ve Maintainer, N.L. (2017) Package ‘AnnotationDbi.’ Bioconductor Package Maintainer.
  • [14] Zhou, Y. ve Zhou, B. ve Pache, L. ve Chang, M. ve Khodabakhshi, A.H. ve Tanaseichuk, O. ve et al. (2019) Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nature Communications. 10 (1), 1523.
  • [15] Dennis, G. ve Sherman, B.T. ve Hosack, D.A. ve Yang, J. ve Gao, W. ve Lane, H.C. ve et al. (2003) DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome biology. 4 (5),.
  • [16] Stark, C. ve Breitkreutz, B.J. ve Reguly, T. ve Boucher, L. ve Breitkreutz, A. ve Tyers, M. (2006) BioGRID: a general repository for interaction datasets. Nucleic acids research. 34 (Database issue), 535–539. [17] Shannon, P. ve Markiel, A. ve Ozier, O. ve Baliga, N.S. ve Al., E. (1971) Cytoscape: A Software Environment for Integrated Models. Genome Research. 13 (22), 426.
  • [18] Chin, C.H. ve Chen, S.H. ve Wu, H.H. ve Ho, C.W. ve Ko, M.T. ve Lin, C.Y. (2014) cytoHubba: Identifying hub objects and sub-networks from complex interactome. BMC Systems Biology.
  • [19] Gungor, M.A. ve Karagoz, I. (2015) The homogeneity map method for speckle reduction in diagnostic ultrasound images. Measurement: Journal of the International Measurement Confederation. 68 100–110.
  • [20] Turanli, B. ve Gulfidan, G. ve Arga, K.Y. (2017) Transcriptomic-Guided Drug Repositioning Supported by a New Bioinformatics Search Tool: geneXpharma. OMICS: A Journal of Integrative Biology. 21 (10), 584–591.
  • [21] Wagner, A.H. ve Coffman, A.C. ve Ainscough, B.J. ve Spies, N.C. ve Skidmore, Z.L. ve Campbell, K.M. ve et al. (2016) DGIdb 2.0: Mining clinically relevant drug-gene interactions. Nucleic Acids Research. 44 (D1), D1036–D1044.
  • [22] Amelio, I. ve Gostev, M. ve Knight, R.A. ve Willis, A.E. ve Melino, G. ve Antonov, A. V. (2014) DRUGSURV: A resource for repositioning of approved and experimental drugs in oncology based on patient survival information. Cell Death and Disease.
  • [23] Islam, T. ve Rahman, R. ve Gov, E. ve Turanli, B. ve Gulfidan, G. ve Haque, A. ve et al. (2018) Drug Targeting and Biomarkers in Head and Neck Cancers: Insights from Systems Biology Analyses. OMICS: A Journal of Integrative Biology. 22 (6), 422–436. [24] Gov, E. ve Kori, M. ve Arga, K.Y. (2017) Multiomics Analysis of Tumor Microenvironment Reveals Gata2 and miRNA-124-3p as Potential Novel Biomarkers in Ovarian Cancer. OMICS A Journal of Integrative Biology. 21 (10), 603–615.
  • [25] Rahman, M.R. ve Petralia, M.C. ve Ciurleo, R. ve Bramanti, A. ve Fagone, P. ve Shahjaman, M. ve et al. (2020) Comprehensive analysis of rna-seq gene expression profiling of brain transcriptomes reveals novel genes, regulators, and pathways in autism spectrum disorder. Brain Sciences. 10 (10), 747.
  • [26] Calimlioglu, B. ve Karagoz, K. ve Sevimoglu, T. ve Kilic, E. ve Gov, E. ve Arga, K.Y. (2015) Tissue-Specific Molecular Biomarker Signatures of Type 2 Diabetes: An Integrative Analysis of Transcriptomics and Protein-Protein Interaction Data. Omics : a journal of integrative biology. 19 (9), 563–573.
  • [27] Karagoz, K. ve Lehman, H.L. ve Stairs, D.B. ve Sinha, R. ve Arga, K.Y. (2016) Proteomic and Metabolic Signatures of Esophageal Squamous Cell Carcinoma. Current cancer drug targets.
  • [28] Turanli, B. ve Karagoz, K. ve Bidkhori, G. ve Sinha, R. ve Gatza, M.L. ve Uhlen, M. ve et al. (2019) Multi-omic data interpretation to repurpose subtype specific drug candidates for breast cancer. Frontiers in Genetics. 10 420.
  • [29] Wang, S. ve Chen, X. (2018) Identification of potential biomarkers in cervical cancer with combined public mRNA and miRNA expression microarray data analysis. Oncology Letters. 47 (9), 755–765.
  • [30] Gulfidan, G. ve Turanli, B. ve Beklen, H. ve Sinha, R. ve Arga, K.Y. (2020) Pan-cancer mapping of differential protein-protein interactions. Scientific Reports. 10 (1), 1–12.
  • [31] Kirn, V. ve Zaharieva, I. ve Heublein, S. ve Thangarajah, F. ve Friese, K. ve Mayr, D. ve et al. (2014) ESR1 promoter methylation in squamous cell cervical cancer. Anticancer Research. 34 (2), 723–727.
  • [32] Matsuda, Y. ve Ueda, J. ve Ishiwata, T. (2012) Fibroblast growth factor receptor 2: Expression, roles, and potential as a novel molecular target for colorectal cancer. Pathology Research International. 2012 574768.
  • [33] Branca, M. ve Ciotti, M. ve Giorgi, C. ve Santini, D. ve Di Bonito, L. ve Costa, S. ve et al. (2007) Up-regulation of proliferating cell nuclear antigen (PCNA) is closely associated with high-risk human papillomavirus (HPV) and progression of cervical intraepithelial neoplasia (CIN), but does not predict disease outcome in cervical cancer. European Journal of Obstetrics and Gynecology and Reproductive Biology. 130 (2), 223–31.
  • [34] K, R. ve C, F. ve K, B. ve Wappenschmidt B, S.R. (2007) Increased risk of cervical cancer in high-risk families with and without mutations in the BRCA1 and BRCA2 genes. Journal of Clinical Oncology. 25.
  • [35] Logé, C. ve Testard, A. ve Thiéry, V. ve Lozach, O. ve Blairvacq, M. ve Robert, J.M. ve et al. (2008) Novel 9-oxo-thiazolo[5,4-f]quinazoline-2-carbonitrile derivatives as dual cyclin-dependent kinase 1 (CDK1)/glycogen synthase kinase-3 (GSK-3) inhibitors: Synthesis, biological evaluation and molecular modeling studies. European Journal of Medicinal Chemistry. 43 (7), 1469–1477.
  • [36] Zhai, Y. ve Kuick, R. ve Nan, B. ve Ota, I. ve Weiss, S.J. ve Trimble, C.L. ve et al. (2007) Gene expression analysis of preinvasive and invasive cervical squamous cell carcinomas identifies HOXC10 as a key mediator of invasion. Cancer Research.
  • [37] Scotto, L. ve Narayan, G. ve Nandula, S. V. ve Arias-Pulido, H. ve Subramaniyam, S. ve Schneider, A. ve et al. (2008) Identification of copy number gain and overexpressed genes on chromosome arm 20q by an integrative genomic approach in cervical cancer: Potential role in progression. Genes Chromosomes and Cancer. 47 (9), 755–65.
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There are 51 citations in total.

Details

Primary Language Turkish
Subjects Engineering
Journal Section Research Articles
Authors

Beste Turanlı 0000-0003-1330-9712

Project Number 119S999
Publication Date December 30, 2021
Published in Issue Year 2021 Volume: 33 Issue: 4

Cite

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 Turanlı B. Rahim Ağzı Kanser Alt-Tiplerine Özgü Moleküler Hedef, Biyoişaretçi Adaylar ve Yeniden Konumlandırılan İlaçların Belirlenmesi. JEPS. December 2021;33(4):537-548. doi:10.7240/jeps.869943
Chicago 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, no. 4 (December 2021): 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 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, 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 2021), 537-548. https://doi.org/10.7240/jeps.869943.
JAMA 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, 2021, pp. 537-48, doi:10.7240/jeps.869943.
Vancouver Turanlı B. Rahim Ağzı Kanser Alt-Tiplerine Özgü Moleküler Hedef, Biyoişaretçi Adaylar ve Yeniden Konumlandırılan İlaçların Belirlenmesi. JEPS. 2021;33(4):537-48.