genel tıp derg

Genel Tıp Dergisi

2602-3741

Selçuk Üniversitesi

10.54005/geneltip.1758107

Clinical Sciences (Other)

Klinik Tıp Bilimleri (Diğer)

Kolon Adenokarsinomunda SLC9A1 (NHE1)’in Prognostik Rolünün İncelenmesi: In Silico Temelli Biyoinformatik-Biyofiziksel Yaklaşım

Exploring the Prognostic Role of SLC9A1 (NHE1) in Colon Adenocarcinoma: In Silico-Based Bioinformatics- biophysical Approach

https://orcid.org/0000-0002-6314-4816

Adalı

Yasemin

Pamukkale University

https://orcid.org/0000-0001-6081-2308

Ozdil

Berrin

SULEYMAN DEMIREL UNIVERSITY

https://orcid.org/0000-0003-4832-0436

Koseler

Aylin

PAMUKKALE ÜNİVERSİTESİ

03 31 2026

36 2026 1 8 08 04 2025 10 06 2025

1990

Genel Tıp Dergisi

Amaç: Sodyum/Hidrojen değiştirici izoform 1’i (NHE1) kodlayan çözücü taşıyıcı ailesi 9 üyesi A1 (SLC9A1), hücre içi pH dengesinin düzenlenmesinde kritik bir rol oynamakta ve kanser progresyonuyla ilişkilendirilmektedir. Ancak, kolon adenokarsinomundaki prognostik ve biyolojik önemi yeterince araştırılmamıştır.Gereç ve Yöntemler: The Cancer Genome Atlas (TCGA-COAD) projesine ait transkriptomik ve klinik veriler kullanılarak, SLC9A1 ekspresyonu ile kolon kanserindeki moleküler değişiklikler arasındaki ilişki incelendi. Hastalar, yüksek ve düşük SLC9A1 ekspresyonuna sahip gruplara ayrıldı. Farklı gen ekspresyonu analizi DESeq2 paketi ile gerçekleştirildi. Hallmark gen setleri kullanılarak gen set zenginleştirme analizi (GSEA), ayrıca Gene Ontology ve Kyoto Encyclopedia of Genes and Genomes (KEGG) veri tabanları aracılığıyla yolak zenginleştirme analizleri yapıldı. Kaplan-Meier sağkalım analizleri ve log-rank testleri ile prognostik değer değerlendirildi. Ek olarak, mikrosatellit instabilitesi (MSI) alt tipleri arasında gen ekspresyon seviyeleri karşılaştırıldı.Bulgular: Diferansiyel ekspresyon analizi, SLC9A1-ekspresyonu yüksek olan tümörlerde 12.789 farklı şekilde eksprese olmuş gen (11.991 yukarı regüle, 798 aşağı regüle) tespit etti. Hallmark GSEA, düzeltilmiş p-değeri eşikleri altında istatistiksel olarak anlamlı bir zenginleşme göstermemekle birlikte, yolak düzeyinde yapılan analizler ribozom biyogenezi ve epitel-mezenkimal geçişin baskılanması gibi biyolojik temaları ön plana çıkardı. Ayrıca Wnt/β-katenin, Notch ve Transforming Growth Factor Beta (TGF-β) sinyal yollarında zenginleşme gözlendi. Sağkalım analizi, SLC9A1 yüksek grubunda genel sağkalımın azaldığına dair istatistiksel olarak anlamlı olmayan bir eğilim gösterdi. Mikrosatellit instabilitesi yüksek (MSI-H) ve mikrosatellit stabil (MSS) tümörler arasında anlamlı bir ekspresyon farkı bulunmadı.Sonuçlar: SLC9A1 ekspresyonu kolon adenokarsinomunda bağımsız bir prognostik biyobelirteç olarak öne çıkmasa da, pH dengesi ve hücresel adaptasyonla ilişkili temel biyolojik yolların düzenlenmesi aracılığıyla tümör progresyonuna katkı sağlayabilir. Mekanistik rolünün ve terapötik potansiyelinin aydınlatılması için fonksiyonel modellerde ek doğrulama çalışmaları gereklidir.

Aim: The solute carrier family 9 member A(SLC9A1), encoding the Na⁺/H⁺ exchanger isoform 1(NHE1), plays a key role in regulating intracellular pH and has been implicated in cancer progression. However, its prognostic and biological relevance in colon adenocarcinoma remains insufficiently explored.Methods: Using transcriptomic and clinical data from The Cancer Genome Atlas(TCGA-COAD), we investigated the association between SLC9A1 expression and molecular alterations in colon cancer. Patients were stratified into high and low SLC9A1 expression groups. Differential gene expression analysis was performed using DESeq2. Gene set enrichment analysis with Hallmark gene sets and pathway enrichment via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes(KEGG) databases were applied. Kaplan-Meier survival analysis and log-rank tests assessed prognostic value. Additionally, expression levels were compared across microsatellite instability(MSI) subtypes.Results: Differential Expression Analysis identified 12,789 differentially expressed genes(11,991 upregulated and 798 downregulated) in SLC9A1-high tumors. Although Hallmark GSEA did not yield statistically significant enrichment under adjusted p-value thresholds, pathway-level analysis highlighted biological themes such as ribosome biogenesis and suppression of epithelialmesenchymal transition. Enrichment was also noted in Wnt/β-catenin, Notch, and Transforming Growth Factor Beta(TGF-β) signaling pathways. Survival analysis showed a non-significant trend toward reduced overall survival in the SLC9A1-high group. No significant expression differences were found between microsatellite instability-high(MSI-H) and microsatellite-stable(MSS) tumors.Conclusions: While SLC9A1 expression is not an independent prognostic biomarker in colon adenocarcinoma, it may contribute to tumor progression through regulation of key pathways linked to pH balance and cellular adaptation. Further validation in functional models is warranted to elucidate its mechanistic role and therapeutic potential.

Colon Adenocarcinoma SLC9A1 Biophysics Bioinformatics

Kolon Adenokarsinomu SLC9A1 Biyofizik Biyoinformatik

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