İzositrat dehidrojenaz 1 ve izositrat dehidrojenaz 2 genlerinin gen ekspresyon değişiklikleri karsinojenezi ve hayatta kalma olasılığını etkiler

Year 2024, Volume: 14 Issue: 1, 370 - 378, 15.03.2024

Esra Bulut Atalay

https://doi.org/10.17714/gumusfenbil.1353355

Abstract

İzositrat dehidrojenaz (IDH), hücre metabolizmasının düzenlenmesinde önemli bir metabolik enzimdir. IDH geni, IDH1, IDH2 ve IDH3 olmak üzere üç protein izoformunu kodlar ve izoformların ekspresyon seviyesi, insan kanser türlerinde değişiklik gösterir. IDH'nin gen ekspresyon seviyesinin incelenmesi, kanser metabolizması alanında kullanılacak yeni bir hedef bulmaya yardımcı olabilecek terapötik bir avantajdır. Bu çalışmanın amacı, biyoinformatik araçlar kullanarak on yaygın insan kanserinde IDH1 ve IDH2 izoformlarının gen ekspresyon seviyesini araştırmaktır. Ek olarak, IDH1 ve IDH2’nin gen ekspresyon seviyesindeki değişikliklerin karsinogenez ve hayatta kalma olasılığı üzerindeki etkisi TCGA veri tabanında depolanan halka açık veriler üzerinde incelenmiştir. Elde edilen sonuçlar, IDH izoformlarının ekspresyonunun dokuya özgü farklılıklar ve heterojen özellik sergilediğini gösterdi. IDH1 ekspresyonu özofagus ve akciğer skuamöz hücreli karsinom ile akciğer ve mide adenokarsinomu tümörlerinde arttı. Mesane ürotelyal, meme ürotelyal ve akciğer skuamöz hücreli karsinomu ve kolon ve akciğer adenokarsinomu, IDH2 ekspresyonunda önemli bir artış sergiledi. IDH izoformlarının ekspresyonu ile çeşitli kanser türlerinin ilerlemesi arasında doğrudan bir ilişki olduğu bulundu. Yüksek IDH1 ekspresyonu, özofagus karsinomu, akciğer ve mide adenokarsinomunda hayatta kalma olasılığının azalmasına yol açtı. Yüksek IDH2 ekspresyon seviyesi, mesane ürotelyal, meme ürotelyal ve akciğer skuamöz hücreli karsinom ve kolon adenokarsinomunda hayatta kalma olasılığının azalmasına yol açtı. Sonuç olarak, tüm veriler IDH1'in özofagus karsinomu, akciğer ve mide adenokarsinomu için ve IDH2'nin mesane ürotelyal, meme ürotelyal ve akciğer skuamöz hücreli karsinom ve kolon adenokarsinomu için bir biyobelirteç olabileceğini gösterdi.

Keywords

Biyoinformatik, Karsinogenez, İzositrat dehidrojenaz 1, İzositrat dehidrojenaz 2

Gene expression changes of isocitrate dehydrogenase 1 and isocitrate dehydrogenase 2 affect carcinogenesis and survival probability

Abstract

Isocitrate dehydrogenase (IDH) is an essential metabolic enzyme in the regulation of cellular metabolism. IDH gene encodes three protein isoforms, IDH1, IDH2, and IDH3, and the expression level of isoforms is altered in human cancer types. Examining the gene expression level of IDH is a therapeutic advantage that could help find a new target to use in cancer metabolism. The present study aimed to explore the gene expression level of IDH1 and IDH2 isoforms in the ten common human cancers using bioinformatic tools. In addition, the effect of gene expression changes on IDH1 and IDH2 on carcinogenesis and survival probability was examined in publicly available data deposited in the TCGA database. The results showed that the expression of IDH isoforms showed tissue-specific differences. IDH1 expression increased in esophageal and lung squamous cell carcinoma and lung and stomach adenocarcinoma tumors. Bladder urothelial, breast urothelial, and lung squamous cell carcinoma, colon, and lung adenocarcinoma displayed a significant upregulation of IDH2 expression. There was a direct relationship between the expression of IDH isoforms and the progression of various cancer types. High IDH1 expression led to decreased survival probability in esophageal carcinoma, lung, and stomach adenocarcinoma. Elevated IDH2 expression level led to decreased survival probability in bladder urothelial, breast urothelial, and lung squamous cell carcinoma and colon adenocarcinoma. In conclusion, all data showed that IDH1 could be a biomarker for esophageal carcinoma, lung and stomach adenocarcinoma, and IDH2 for bladder urothelial, breast urothelial, and lung squamous cell carcinoma, and colon adenocarcinoma.

Keywords

Bioinformatic, Carcinogenesis, Isocitrate dehydrogenase 1, Isocitrate dehydrogenase 2

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