Identification KCNE4 and DNASE1L3 for Prognostic Utility in Colorectal Cancer: A Bioinformatics Analysis

Objective: Immunotherapy has improved the prognosis of cancer patients who did not benefit from conventional treatment and decreased mortality, which has become an effective treatment for multiple carcinomas in their advanced stages. Patients with colorectal cancer (CRC) were mostly in the state of mismatch repair-proficient or microsatellite stability, with limited benefit in immunotherapy. Hence, immunotherapy strategies for CRC still need to be explored continuously. Methods: Based on comprehensive analysis of the immune infiltration associated genes in the Cancer Genome Atlas (TCGA) database and differential genes for the progression and metastasis of CRC in the Gene Expression Omnibus (GEO) database, as well as validation analysis on several online databases, we obtained two genes (KCNE4 and DNASE1L3) as novel immune-related molecules for CRC. Results: High expression of KCNE4 and DNASE1L3 were significantly correlated with CRC progression and prognosis, and were strongly associated with the infiltration of different types of macrophages in the CRC tumor microenvironment. In addition, we analysed the guidance value of KCNE4 and DNASE1L3 in anti-PD-1 therapy using data from the IMvigor210 group, and predicted the significant value of KCNE4 and DNASE1L3 in CRC immunotherapy by analyzing the correlation of KCNE4 and DNASE1L3 with the expression of CRC immune checkpoint markers. Conclusions: We hypothesized that DNASE1L3 and KCNE4 would be potential prognostic biomarkers and predictors of immunotherapy in CRC. Our results may serve as an indication of survival prognosis and provide a new assessment indicator for the choice of immunotherapy for CRC patients.