Exploring the Prognostic Role of SLC9A1 (NHE1) in Colon Adenocarcinoma

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.