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GLİAL BEYİN TÜMÖRLERİNİN İLERLEMESİNDE ROL OYNAYAN GEN İFADE DEĞİŞİKLİKLERİ VE MERKEZİ GENLERİNİN İNCELENMESİ

Yıl 2023, Cilt: 6 Sayı: 3, 380 - 389, 21.10.2023

Nurhan Külcü Sarıkaya Deniz Sünnetçi Akkoyunlu

Öz

Amaç: Gliomanın oldukça agresif bir formu olan glioblastoma, tüm malign beyin tümörlerinin %80'ini ve tüm gliomaların %55'ini oluşturan en yaygın malign beyin tümörüdür. Tedaviye rağmen glioblastomalı hastalar için medyan sağkalım bir yıldan biraz fazladır. Bu çalışma, gen ekspresyon farklılıklarının ve yollarının glioma gelişimi ve ilerlemesindeki etkisini anlamayı amaçlamaktadır.

Yöntem: Çalışmaya Gene Expression Omnibus (GEO) veritabanından 150 glioma örneği ve 15 normal beyin doku örneği dahil edildi. Normal doku ile derece II, III ve IV glioma dokuları arasında diferansiyel olarak eksprese edilen genleri (DEG'ler) elde etmek için GeneSpring yazılımı kullanıldı. DEG'ler, GO ve KEGG yolak analizi için DAVID arayüzü kullanılarak analiz edildi. Cytoscape yazılımındaki STRING uygulaması kullanılarak her derecede en çok bağlantıya sahip 15 gen merkez gen olarak seçildi.

Bulgular: DEG'ler nöroaktif ligand-reseptör etkileşimi, sistemik lupus eritematozus, komplement ve pıhtılaşma kaskadları ve GABAerjik sinaps ile ilişkilendirildi. Toplam 21 gen (ALB, CXCL8, EGF, EGFR, FN1, GAPDH, GNG13, GNG7, GNGT1, IL10, IL6, INS, KNG1, MAPK1, MYC, NOTCH1, SRC, STAT3, TNF, TP53 ve VEGFA) merkezi gen olarak belirlendi. Merkezi genler arasında INS geni, bütün derecelerde en yüksek bağlantı düzeyine sahip olduğu bulundu. IL6, düşük sağkalım ile ilişkilendirildi ve yüksek dereceli gliomalarda rol oynadığı düşünüldü. STAT3 ve düşük sağkalımla ilişkili EGF, derece IV'de tespit edildi. İnsan sitomegalovirüsü (HCMV) enfeksiyonu, merkez genlerin KEGG analizine göre yüksek dereceli gliomalarda en anlamlı yol olarak ortaya çıktı.

Sonuç: Bu çalışmanın bulguları, gliomalar için potansiyel prognostik ve terapötik hedefleri işaret etmektedir.

Anahtar Kelimeler

Glioma gen ekspresyonu merkezi genler entegre analiz

Kaynakça

  • Sharma P, Debinski W. Receptor-targeted glial brain tumor therapies. Int J Mol Sci. 2018;19(11):3326. doi:10.3390/ ijms19113326
  • Ohgaki H, Kleihues P. Epidemiology and etiology of gliomas. Acta Neuropathol. 2005;109(1):93-108. doi:10. 1007/s00401-005-0991-y
  • Hsu JB-K, Chang T-H, Lee GA, Lee T-Y, Chen C-Y. Identification of potential biomarkers related to glioma survival by gene expression profile analysis. BMC Med Genomics. 2019;11:7. doi:10.1186/s12920-019-0479-6
  • Nazarenko I, Hede S-M, He X, et al. PDGF and PDGF receptors in glioma. Ups. J. Med. Sci. 2012;117(2):99-112. doi:10.3109/03009734.2012.665097
  • Olson JJ, Barnett D, Yang J, Assietti R, Cotsonis G, James CD. Gene amplification as a prognostic factor in primary brain tumors. Clin Cancer Res. 1998;4(1):215-222.
  • Shinojima N, Tada K, Shiraishi S, et al. Prognostic value of epidermal growth factor receptor in patients with glioblastoma multiforme. Cancer Res. 2003;63(20):6962-6970.
  • Sereika M, Urbanaviciute R, Tamasauskas A, Skiriute D, Vaitkiene P. GFAP expression is influenced by astrocytoma grade and rs2070935 polymorphism. J. Cancer. 2018;9(23):4496-4502. doi:10.7150/jca.26769
  • Her N-G, Oh J-W, Oh YJ, et al. Potent effect of the MDM2 inhibitor AMG232 on suppression of glioblastoma stem cells. Cell Death Dis. 2018;9(8):792. doi:10.1038/s41419-018-0825-1
  • Yin W, Tang G, Zhou Q, et al. Expression profile analysis identifies a novel five-gene signature to improve prognosis prediction of glioblastoma. Front. Genet. 2019;10:419. doi:10.3389/fgene.2019.00419
  • Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z. Gepia: A web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017;45(W1):W98-W102. doi:10.1093/nar/gkx247
  • Pal J, Patil V, Kumar A, Kaur K, Sarkar C, Somasundaram K. Loss-of-function mutations in calcitonin receptor (calcr) identify highly aggressive glioblastoma with poor outcome. Clin Cancer Res. 2018;24(6):1448-1458. doi:10.1158/1078-0432.ccr-17-1901
  • Guglietta S, Rescigno M. Hypercoagulation and complement: Connected players in tumor development and metastases. Semin. Immunol. 2016;28(6):578-586. doi:10.1016/j.smim.2016.10.011
  • Shi T, Chen J, Li J, Yang B, Zhang Q. Identification of key gene modules and pathways of human glioma through Coexpression Network. J. Cell. Physiol. 2018;234(2):1862-1870. doi:10.1002/jcp.27059
  • Hu K, Li J, Wu G, et al. The novel roles of virus infection-associated gene CDKN1A in chemoresistance and immune infiltration of glioblastoma. Aging. 2021;13(5):6662-6680. doi:10.18632/aging.202519
  • Yang Y, Ren L, Li W, et al. GABAergic signaling as a potential therapeutic target in cancers. Biomed. Pharmacother. 2023;161:114410. doi:10.1016/j.biopha.2023.114410
  • Vigneri R, Sciacca L, Vigneri P. Rethinking the relationship between insulin and cancer. Trends Endocrinol. Metab. 2020;31(8):551-560. doi:10.1016/j.tem.2020.05.004
  • Vigneri R, Goldfine ID, Frittitta L. Insulin, insulin receptors, and cancer. J. Endocrinol. Invest. 2016;39(12):1365-1376. doi:10.1007/s40618-016-0508-7
  • Menziani, M.C., Fanelli, F. and De Benedetti, P.G. (1997) ‘Theoretical investigation of IL-6 multiprotein receptor assembly’, Proteins: Structure, Function, and Genetics, 29(4), pp. 528–548. doi:10.1002/(sici)1097-0134(199712) 29:4<528::aid-prot12>3.0.co;2-o.
  • Fisher, D.T., Appenheimer, M.M. and Evans, S.S. (2014) ‘The two faces of IL-6 in the tumor microenvironment’, Seminars in Immunology, 26(1), pp. 38–47. doi:10.1016/ j.smim.2014.01.008.
  • Wang, H. et al. (2009) ‘Targeting interleukin 6 signaling suppresses glioma stem cell survival and tumor growth’, Stem Cells, 27(10), pp. 2393–2404. doi:10.1002/stem.188.
  • Wang M, Zhang Y, Liu M, et al. Inhibition of STAT3 signaling as critical molecular event in HUC-MSCs suppressed Glioblastoma Cells. J. Cancer. 2023;14(4):611-627. doi:10. 7150/jca.77905
  • Chen Z, Yuan SJ, Li K, et al. Doxorubicin-polyglycerol-nanodiamond conjugates disrupt STAT3/IL-6-mediated reciprocal activation loop between glioblastoma cells and astrocytes. J. Control. Release. 2020;320:469-483. doi:10. 1016/j.jconrel.2020.01.044
  • Kim JE, Patel M, Ruzevick J, Jackson CM, Lim M. STAT3 activation in glioblastoma: Biochemical and therapeutic implications. Cancers. 2014;6(1):376-395. doi:10.3390/ cancers6010376
  • Pudełek M, Król K, Catapano J, Wróbel T, Czyż J, Ryszawy D. Epidermal growth factor (EGF) augments the invasive potential of human glioblastoma multiforme cells via the activation of collaborative EGFR/ROS-dependent signaling. Int. J. Mol. Sci. 2020;21(10):3605. doi:10.3390/ijms211036 05.
  • Chen XC, Wei XT, Guan JH, Shu H, Chen D. EGF stimulates glioblastoma metastasis by induction of matrix metalloproteinase-9 in an EGFR-dependent mechanism. Oncotarget. 2017;8(39):65969-65982. doi:10.18632/ oncotarget.19622
  • Falcão, A.S. et al. Mechanisms of human cytomegalovirus infection with a focus on epidermal growth factor receptor interactions. Rev. Med. Virol, 2017;27:6. doi:10.1002/rmv. 1955.
  • Zhu X, Hu B, Hu M, Qian D, Wang B. Human cytomegalovirus infection enhances invasiveness and migration of glioblastoma cells by epithelial-to-mesenchymal transition. Int J Clin. Exp. Pathol. 2020;13(10):2637-2647.
  • Hochhalter CB, Carr, C, O’Neil B, Ware ML, Strong MJ. The association between human cytomegalovirus and Glioblastomas: A Review. Neuroimmunol. Neuroinflammation. 2017;4(6):96. doi:10.20517/2347-86 59.2017.10.
  • Fiallos E, Judkins J, Matlaf L, et al. Human cytomegalovirus gene expression in long-term infected glioma stem cells. PLoS One. 2014; 9(12):e166178. doi:10.1371/journal. pone.0116178.
  • Price RL, Chiocca EA. Modeling cytomegalovirus infection in mouse tumor models. Front. Oncol. 2015;5:61. doi:10.3389/fonc.2015.00061.

INVESTİGATİNG GENE EXPRESSİON CHANGES AND HUB GENES PLAYİNG A ROLE İN THE PROGRESSİON OF GLİAL BRAİN TUMORS

Yıl 2023, Cilt: 6 Sayı: 3, 380 - 389, 21.10.2023

Nurhan Külcü Sarıkaya Deniz Sünnetçi Akkoyunlu

Öz

Anahtar Kelimeler

Glioma gene expression hub genes integrated analysis

Kaynakça

  • Sharma P, Debinski W. Receptor-targeted glial brain tumor therapies. Int J Mol Sci. 2018;19(11):3326. doi:10.3390/ ijms19113326
  • Ohgaki H, Kleihues P. Epidemiology and etiology of gliomas. Acta Neuropathol. 2005;109(1):93-108. doi:10. 1007/s00401-005-0991-y
  • Hsu JB-K, Chang T-H, Lee GA, Lee T-Y, Chen C-Y. Identification of potential biomarkers related to glioma survival by gene expression profile analysis. BMC Med Genomics. 2019;11:7. doi:10.1186/s12920-019-0479-6
  • Nazarenko I, Hede S-M, He X, et al. PDGF and PDGF receptors in glioma. Ups. J. Med. Sci. 2012;117(2):99-112. doi:10.3109/03009734.2012.665097
  • Olson JJ, Barnett D, Yang J, Assietti R, Cotsonis G, James CD. Gene amplification as a prognostic factor in primary brain tumors. Clin Cancer Res. 1998;4(1):215-222.
  • Shinojima N, Tada K, Shiraishi S, et al. Prognostic value of epidermal growth factor receptor in patients with glioblastoma multiforme. Cancer Res. 2003;63(20):6962-6970.
  • Sereika M, Urbanaviciute R, Tamasauskas A, Skiriute D, Vaitkiene P. GFAP expression is influenced by astrocytoma grade and rs2070935 polymorphism. J. Cancer. 2018;9(23):4496-4502. doi:10.7150/jca.26769
  • Her N-G, Oh J-W, Oh YJ, et al. Potent effect of the MDM2 inhibitor AMG232 on suppression of glioblastoma stem cells. Cell Death Dis. 2018;9(8):792. doi:10.1038/s41419-018-0825-1
  • Yin W, Tang G, Zhou Q, et al. Expression profile analysis identifies a novel five-gene signature to improve prognosis prediction of glioblastoma. Front. Genet. 2019;10:419. doi:10.3389/fgene.2019.00419
  • Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z. Gepia: A web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017;45(W1):W98-W102. doi:10.1093/nar/gkx247
  • Pal J, Patil V, Kumar A, Kaur K, Sarkar C, Somasundaram K. Loss-of-function mutations in calcitonin receptor (calcr) identify highly aggressive glioblastoma with poor outcome. Clin Cancer Res. 2018;24(6):1448-1458. doi:10.1158/1078-0432.ccr-17-1901
  • Guglietta S, Rescigno M. Hypercoagulation and complement: Connected players in tumor development and metastases. Semin. Immunol. 2016;28(6):578-586. doi:10.1016/j.smim.2016.10.011
  • Shi T, Chen J, Li J, Yang B, Zhang Q. Identification of key gene modules and pathways of human glioma through Coexpression Network. J. Cell. Physiol. 2018;234(2):1862-1870. doi:10.1002/jcp.27059
  • Hu K, Li J, Wu G, et al. The novel roles of virus infection-associated gene CDKN1A in chemoresistance and immune infiltration of glioblastoma. Aging. 2021;13(5):6662-6680. doi:10.18632/aging.202519
  • Yang Y, Ren L, Li W, et al. GABAergic signaling as a potential therapeutic target in cancers. Biomed. Pharmacother. 2023;161:114410. doi:10.1016/j.biopha.2023.114410
  • Vigneri R, Sciacca L, Vigneri P. Rethinking the relationship between insulin and cancer. Trends Endocrinol. Metab. 2020;31(8):551-560. doi:10.1016/j.tem.2020.05.004
  • Vigneri R, Goldfine ID, Frittitta L. Insulin, insulin receptors, and cancer. J. Endocrinol. Invest. 2016;39(12):1365-1376. doi:10.1007/s40618-016-0508-7
  • Menziani, M.C., Fanelli, F. and De Benedetti, P.G. (1997) ‘Theoretical investigation of IL-6 multiprotein receptor assembly’, Proteins: Structure, Function, and Genetics, 29(4), pp. 528–548. doi:10.1002/(sici)1097-0134(199712) 29:4<528::aid-prot12>3.0.co;2-o.
  • Fisher, D.T., Appenheimer, M.M. and Evans, S.S. (2014) ‘The two faces of IL-6 in the tumor microenvironment’, Seminars in Immunology, 26(1), pp. 38–47. doi:10.1016/ j.smim.2014.01.008.
  • Wang, H. et al. (2009) ‘Targeting interleukin 6 signaling suppresses glioma stem cell survival and tumor growth’, Stem Cells, 27(10), pp. 2393–2404. doi:10.1002/stem.188.
  • Wang M, Zhang Y, Liu M, et al. Inhibition of STAT3 signaling as critical molecular event in HUC-MSCs suppressed Glioblastoma Cells. J. Cancer. 2023;14(4):611-627. doi:10. 7150/jca.77905
  • Chen Z, Yuan SJ, Li K, et al. Doxorubicin-polyglycerol-nanodiamond conjugates disrupt STAT3/IL-6-mediated reciprocal activation loop between glioblastoma cells and astrocytes. J. Control. Release. 2020;320:469-483. doi:10. 1016/j.jconrel.2020.01.044
  • Kim JE, Patel M, Ruzevick J, Jackson CM, Lim M. STAT3 activation in glioblastoma: Biochemical and therapeutic implications. Cancers. 2014;6(1):376-395. doi:10.3390/ cancers6010376
  • Pudełek M, Król K, Catapano J, Wróbel T, Czyż J, Ryszawy D. Epidermal growth factor (EGF) augments the invasive potential of human glioblastoma multiforme cells via the activation of collaborative EGFR/ROS-dependent signaling. Int. J. Mol. Sci. 2020;21(10):3605. doi:10.3390/ijms211036 05.
  • Chen XC, Wei XT, Guan JH, Shu H, Chen D. EGF stimulates glioblastoma metastasis by induction of matrix metalloproteinase-9 in an EGFR-dependent mechanism. Oncotarget. 2017;8(39):65969-65982. doi:10.18632/ oncotarget.19622
  • Falcão, A.S. et al. Mechanisms of human cytomegalovirus infection with a focus on epidermal growth factor receptor interactions. Rev. Med. Virol, 2017;27:6. doi:10.1002/rmv. 1955.
  • Zhu X, Hu B, Hu M, Qian D, Wang B. Human cytomegalovirus infection enhances invasiveness and migration of glioblastoma cells by epithelial-to-mesenchymal transition. Int J Clin. Exp. Pathol. 2020;13(10):2637-2647.
  • Hochhalter CB, Carr, C, O’Neil B, Ware ML, Strong MJ. The association between human cytomegalovirus and Glioblastomas: A Review. Neuroimmunol. Neuroinflammation. 2017;4(6):96. doi:10.20517/2347-86 59.2017.10.
  • Fiallos E, Judkins J, Matlaf L, et al. Human cytomegalovirus gene expression in long-term infected glioma stem cells. PLoS One. 2014; 9(12):e166178. doi:10.1371/journal. pone.0116178.
  • Price RL, Chiocca EA. Modeling cytomegalovirus infection in mouse tumor models. Front. Oncol. 2015;5:61. doi:10.3389/fonc.2015.00061.
Toplam 30 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Biyoinformatik ve Hesaplamalı Biyoloji (Diğer)
Bölüm Araştırma Makaleleri
Yazarlar

Nurhan Külcü Sarıkaya 0000-0003-4140-1399

Deniz Sünnetçi Akkoyunlu 0000-0001-9297-8222

Yayımlanma Tarihi 21 Ekim 2023
Gönderilme Tarihi 10 Ağustos 2023
Kabul Tarihi 11 Eylül 2023
Yayımlandığı Sayı Yıl 2023 Cilt: 6 Sayı: 3

Kaynak Göster

AMA Külcü Sarıkaya N, Sünnetçi Akkoyunlu D. INVESTİGATİNG GENE EXPRESSİON CHANGES AND HUB GENES PLAYİNG A ROLE İN THE PROGRESSİON OF GLİAL BRAİN TUMORS. Acta Med Nicomedia. Ekim 2023;6(3):380-389.
 Kapak Resmi İndir

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