KCNC3 acts as a potential biomarker that is involved in the prognosis and tumor immune microenvironment in colorectal cancer

Background: Colorectal cancer (CRC), the most common primary tumor in the gastrointestinal system, is a leading cause of death due to cancer worldwide. CRC is a heterogeneous disease that is associated with several genetic or somatic mutations. Cancer immunotherapy has become a novel and revolutionary method of treatment for patients with advanced tumors. However, effective biomarkers that can reflect the response of CRC patients to immunotherapy have still not been identified. In this study, we aimed to assess the clinical predictive value of KCNC3 in patients with CRC. Methods The correlation between KCNC3 expression levels and CRC progression was explored and validated using data from TCGA and patient samples from our hospital. Univariate and multivariate cox regression models were developed to determine the predictive value of KCNC3 on the prognosis of patients with CRC. Thereafter, the relationship between KCNC3 and immune activation was then analyzed. Finally, we predicted the immunotherapy response in both the high and low KCNC3 expression subgroups. Results In this study, patients with high expression of KCNC3 showed shorter OS (overall survival) than patients with low KCNC3 expression. Data from TCGA database and clinical patient parameters showed that high KCNC3 expression was associated with tumor immune infiltration and poor prognosis of CRC. Furthermore, we found that KCNC3 could be used to stratify CRC patients into high and low KCNC3 expression subgroups, which exhibit different clinical outcomes and immune activation status. At the RNA level data from TCGA showed that KCNC3 expression was positively correlated with the infiltration levels of CD4 + cells, Tregs, and MDSC, which contributed to the formation of an immunosuppressive immune microenvironment (TME) for effective cancer immunotherapy. In addition, the high expression of KCNC3 was accompanied by the upregulation of immune checkpoint molecules, including PDCD1, LAG3, FOXP3, and CTLA4, which stimulated tumor cells to evade immune surveillance. Our clinical data also suggest that high KCNC3 expression is closely associated with CTLA4 and LAG3. Finally, we demonstrated that CRC patients with a high KCNC3 expression level had better immunotherapy responses. Conclusions This study demonstrated that the high expression of KCNC3 confers with immunosuppressive microenvironment that can promote tumor progression and can be used to predict the poor clinical outcome of CRC patients. In conclusion, KCNC3 is a novel predictor for clinical prognosis and response to immunotherapy in CRC.