| Objective Use bioinformatics methods to analyze the mutations of DNA polymerase ε (POLE) and DNA polymerase δ1 (POLD1) in colorectal cancer (CRC), and to explore its influence on the prognosis of CRC and immunotherapy. Methods Based on the data set of the TCGA database, the cBioPortal tool is used to analyze the changes and prognosis of POLE/POLD1 in pan-cancer. Then the two scoring systems of MSI sensor and MINTIS are used to detect microsatellite instability (MSI) in POLE/POLD1 wild-type and mutant-type in CRC patients. The TIMER database was used to analyze the correlation between CRC and POLE/POLD1 mutation in the term of immune cell infiltration and immune checkpoint expression. Results The mutation frequency of the POLE/POLD1 gene in CRC is 6%, predominantly consisting of missense mutations. In pan-cancer, patients with mutations in POLE showed significantly prolonged progression-free survival (P<0.001), disease-free survival (P<0.001), and disease-specific survival (P=0.0178). The mutated type of CRC with POLE/POLD1 alterations exhibited significantly higher MSI percentage compared to the wild-type CRC patients (P<0.001), along with a significant upregulation of immune checkpoint-related genes CD274, HAVCR2, PDCD1, CTLA4, LAG3, TIGIT, and PDCD1LG2 expression. The expression of POLE and POLD1 genes in CRC is significantly correlated with TMB. Furthermore, the mutation in POLE/POLD1 in CRC is associated with the infiltration of immune cells such as CD8+ T cells, neutrophils, and dendritic cells. Conclusion Mutations on POLE/POLD1 are relative common in CRC, and mutations of POLD1 are related to the prognosis of patients in pan-cancer. Mutations on the POLE/POLD1 gene may cause increased MSI, up-regulation of immune checkpoint expression, and increased immune cell infiltration, which may become a new target for immunotherapy. |
