β1-Integrin–Wnt/β-Katenin Etkileşiminin Pan-Kanser Biyoinformatik Analizi ve Terapötik Potansiyeli

Yıl 2025, Cilt: 1 Sayı: 2, 41 - 47, 29.07.2025

Seçil Eroğlu , Safiah Olabi , Oznur Bayraktar Ekmekcigil

Öz

Hücre adezyonunu düzenleyen sinyal mekanizmalarındaki bozuklukların kanser bağlamında anlaşılması, adezyon hedefli tedavilerin klinik uygulamalarda güvenli ve etkili bir şekilde kullanılabilmesi açısından büyük önem taşımaktadır. Hücre dışı matrikse bağlanan temel adezyon reseptörlerinden biri olan β1-integrin, proliferasyon, hücre döngüsü ilerlemesi, apoptoz ve hücre göçü gibi birçok hayati süreci kontrol etmektedir. β1-integrin sinyal ağı oldukça karmaşık olup, çok sayıda tümörojenik yolla kesişmektedir. Bu nedenle, artmış β1-integrin aktivitesinin pek çok kanser türünde hastalık progresyonu ve tedavi direnci ile ilişkili bulunması şaşırtıcı değildir.
Bu çalışmada, ICGC/TCGA (2020) veritabanına ait 2.565 tümör örneği üzerinden bir pan-kanser analizi gerçekleştirilmiş ve β1-integrin ile KEGG map05200’de tanımlanmış 106 kanser ilişkili genlerdeki genetik değişimler incelenmiştir. cBioPortal arayüzü kullanılarak OncoPrint, mutasyon, kopya sayı değişikliği (CNA), karşılıklı dışlayıcılık ve yolak zenginleştirme analizleri yürütülmüştür.
Veriler, β1-integrin ile ilişkili olarak en sık değişikliğe uğrayan yolun Wnt sinyal yolu olduğunu göstermiştir. Ayrıca karşılıklı dışlayıcılık analizleri sonucunda, β1-integrin ile Wnt, LRP5, LRP6 ve FZD gen çiftleri arasında anlamlı düzeyde birlikte görülme (co-occurrence) saptanmıştır (p < 0.001; iki yönlü Fisher exact testi). Bu bulgular, β1-integrin ile Wnt/β-katenin yolları arasında anlamlı bir ilişki olduğunu ortaya koymaktadır. β1-integrinde meydana gelen genetik değişimlerin Wnt/β-katenin aktivasyonunu tetikleyip tetiklemediği ve bu durumun sağkalım ile metastaz üzerindeki etkileri ilerleyen çalışmalarda detaylı olarak incelenecektir.

Anahtar Kelimeler

β1-integrin , Wnt sinyal yolağı , Pan-kanser analiz , Yolak zenginleştirme

A Pan-Cancer Bioinformatic Analysis of β1-Integrin–Wnt/β-Catenin Crosstalk and Its Potential Therapeutic Relevance

Öz

Understanding adhesion receptor signalling dysregulation in cancer settings is vital for the effective and safe incorporation of adhesion-targeted therapeutics in the clinic. β1-integrin is a major extracellular matrix adhesion receptor that has been shown to control important processes such as proliferation, cell cycle progression, apoptosis and cell migration. β1-integrin signalling pathway is complex and can crosstalk with many tumorigenic pathways. It is therefore not surprising that enhanced β1-integrin signalling has been reported to correlate with progression and therapy resistance in many types of cancers. Therefore, a complete understanding of the pathways and genes altered in all cancer types is essential to identify novel therapeutic options specific for certain cancer types. In this study, a pan-cancer analysis was performed to identify alterations of β1-integrin and most dysregulated cancer-related genes (106 genes, Kegg map05200) using 2565 patients whole genomes data (ICGC/TCGA, 2020). OncoPrint, mutations, copy number alterations (CNA), mutual exclusivity and pathway enrichment were conducted using cBioPortal. PathwayMapper, an interactive graphical editing tool allowing collaborative curation was used to view altered genes and pathways with alteration frequencies. Pathway enrichment analyses related to genetic alterations identified the Wnt signaling was the most frequently altered pathway. Mutual exclusivity analyses showed that β1-integrin-Wnt; β1-integrin-LRP5/LRP6 and β1-integrin-FZD pairs exhibited co-occurrence, two sided fisher exact test indicates p < 0.001. This has shown a link between β1-integrin and Wnt/β-catenin pathways. Genetic alterations of β1-integrin receptor, whether these mutations will cause an activation of the Wnt/β-catenin pathway and their effects on overall survival and metastasis will be further examined.

Anahtar Kelimeler

β1-integrin , Wnt signaling , Pan-cancer , Pathway enrichment

Kaynakça

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