KCNJ11 as a prognostic and therapeutic target in colon adenocarcinoma

Colorectal cancer (CRC) continues to pose a significant global health challenge. While it is associated with metabolic disorders, the role of KCNJ11 in colon adenocarcinoma (COAD) remains unclear. This study aims to systematically analyze the biological role of KCNJ11 in COAD using bioinformatics.

In this study, we systematically analyzed KCNJ11 expression in COAD using data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx). To evaluate its diagnostic and prognostic potential, we employed Kaplan-Meier (KM) survival curves and receiver operating characteristic (ROC) curves. Additionally, we identified KCNJ11-associated biological pathways through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA). Immune infiltration levels were assessed using CIBERSORT, and correlations with immune checkpoint markers were examined. Drug sensitivity was further investigated using the Genomics of Drug Sensitivity in Cancer (GDSC) database.

Our results demonstrated that KCNJ11 expression was significantly upregulated in COAD tissues compared to normal controls. High KCNJ11 expression was strongly correlated with reduced overall survival. ROC analysis revealed high diagnostic accuracy, with area under the curve (AUC) values of 0.866 and 0.877 for the training and validation cohorts, respectively. Immune infiltration analysis indicated a significant association between elevated KCNJ11 expression and increased macrophage infiltration. Moreover, KCNJ11 expression exhibited a negative correlation with immune checkpoint markers CD274 [programmed death-ligand 1 (PD-L1)] and HAVCR2 (TIM-3), but a positive correlation with CTLA-4. KCNJ11 levels were also linked to sensitivity to multiple anticancer agents. Pathway enrichment analyses suggested that high KCNJ11 expression was associated with activated ribosome biogenesis and MYC signaling pathways.

Collectively, our findings establish KCNJ11 as a promising molecular biomarker for COAD diagnosis, prognosis prediction, and potential targeted therapeutic intervention.