High KCNJ14 expression is associated with an immunosuppressive tumor microenvironment and advanced pathological features: An RNA in situ hybridization-based analysis of colorectal carcinoma

Colorectal carcinoma (CRC) remains one of the leading causes of cancer-related deaths worldwide, and there is a lack of reliable biomarkers to predict tumor progression and the immune microenvironment. KCNJ14 is a member of the inwardly rectifying potassium channel family that has recently been implicated in tumor progression and immune suppression; however, its clinical significance and spatial expression patterns in CRC remain unclear. We evaluated KCNJ14 mRNA expression by RNA in situ hybridization using an RNAscope on a tissue microarray of 259 CRC cases. We assessed the associations between KCNJ14 expression and clinicopathological features, tumor-infiltrating CD4⁺, CD8⁺, and FOXP3⁺ cells, and patient outcomes. We also performed single-cell RNA sequencing analysis to determine the cell type-specific expression of KCNJ14. KCNJ14 expression was predominantly observed in cancer cells, with high expression identified in 36 cases. High KCNJ14 expression was significantly associated with lymphatic invasion, venous invasion, lymph node metastasis, and advanced disease stage. High KCNJ14 expression was also correlated with decreased intratumoral infiltration of CD4⁺ and CD8⁺ T cells, as well as lower tumor-infiltrating lymphocyte scores, indicating an immunosuppressive tumor microenvironment. In contrast, there were no significant associations between KCNJ14 expression and FOXP3⁺ cell infiltration, overall survival, or recurrence-free survival. This study is the first to demonstrate that high KCNJ14 expression is associated with an immunosuppressive tumor microenvironment and advanced pathological features in CRC. Although KCNJ14 is not an independent prognostic factor, it may serve as a potential indicator of an immunosuppressive tumor microenvironment and be a novel therapeutic target.