SLC9A9 links tumor immune infiltration to therapeutic response in colorectal cancer with emphasis on mismatch repair proficient subtype

Immunotherapy has revolutionized colorectal cancer (CRC) treatment, however, predictive biomarkers for mismatch repair proficient (pMMR) tumors remain scarce. The involvement of the SLC9A9 (solute carrier family 9 member A9) gene in the tumor immune microenvironment is poorly understood. We analyzed publicly available gene expression datasets to assess SLC9A9 expression levels in CRC patients. The relationships between SLC9A9 expression and lymphocyte infiltration, specifically CD8 + and CD4 + T cells, were examined using correlation and regression analyses. Expression of SLC9A9 was notably higher in normal CRC tissues compared to the adjacent tumor tissues, particularly among pMMR CRC patients. Moreover, a significant association was found between SLC9A9 expression and lymphocyte infiltration in these pMMR patients. Interestingly, pMMR patients exhibiting high SLC9A9 expression showed enhanced sensitivity to immunotherapy compared to their counterparts with low SLC9A9 expression. Our study highlights the prognostic value of SLC9A9 in pMMR CRC and its correlation with lymphocyte infiltration, particularly CD8 + and CD4 + T cells. These results provide a foundation for further investigation into the mechanistic link between SLC9A9 expression and tumor immunity, potentially facilitating the creation of innovative therapeutic approaches for pMMR CRC patients. Collectively, SLC9A9 may serve as a novel immune checkpoint to assess the efficacy of immunotherapy and predict therapeutic outcomes in pMMR CRC patients.