POLE/POLD1 Mutation in Colorectal Cancer and Its Relation with Immunotherapy and Prognosis of Patients:Analysis Based on Bioinformatics
[Objective]To investigate the mutations of DNA polymerase e(POLE)and DNA poly-merase δ1(POLD1)in colorectal cancer(CRC)and their relation with immunotherapy and prognosis of patients.[Methods]Using The Cancer Genome Atlas(TCGA)database,the mutations of POLE/POLD1 gene and prognosis of pan-cancer patients were analyzed with the cBioPortal tool.The mi-crosatellite instability(MSI)of wild-type and mutant-type POLE/POLD1 of CRC patients were de-tected by the two scoring systems of MSIsensor and MANTIS.The correlation of POLE/POLD1 mutation with immune cell infiltration and immune checkpoint expression in CRC was analyzed by the TIMER database.[Results]The mutation frequency of the POLE/POLD1 gene in CRC was 6％,predominantly consisting of missense mutations.In pan-cancer,patients with mutations in POLE showed significantly prolonged progression-free survival(PFS)(P＜0.001),disease-free sur-vival(DFS)(P＜0.001),and disease-specific survival(DSS)(P=0.017 8).The CRC patients with mu-tated type of POLE/POLD1 exhibited a significantly higher MSI percentage and up-regulated ex-pression of immune checkpoint-related genes CD274,HAVCR2,PDCD1,CTLA4,LAG3,TIGIT and PDCD1LG2,compared to CRC patients with the wild-type(P＜0.001).The expression of POLE and POLD1 genes in CRC was significantly correlated with tumor mutation burden.Furthermore,the mutation in POLE/POLD1 in CRC was associated with the infiltration of immune cells such as CD8+T cells,neutrophils and dendritic cells.[Conclusion]Mutations on POLE/POLD1 are rela-tive 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-regulated expression of immune checkpoint genes,and increased immune cell infiltration,indicating that POLE/POLD1 gene might be used as a novel target for immunotherapy.
POLE mutationPOLD1 mutationcolorectal neoplasmsbioinformaticsimmunity
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