| Objective This study attempted to identify the mechanisms by which the MCM6 gene affects the process and prognosis of cervical cancer from an immunological perspective,and to assess whether the gene might be a potential prognostic biomarker for cervical cancer,diagnose and predict disease progression,and guide clinical treatment options for cervical cancer by analyzing the differential expression of the MCM6 gene in patients with cervical cancer.Methods Based on The Cancer Genome Atlas(TCGA)database,we compared the differences in MCM6 expression between cervical cancer tissue and normal cervical tissue;analyzed the relationship between MCM6 expression and clinical characteristics of cervical cancer patients;analyzed the correlation between MCM6 expression levels and mismatch repair(MMR)genes,homologous recombination repair(HRR)genes and with HRR gene signature(HRR Signature);further analyzed the expression of some Immune Checkpoint Molecules(ICMs)in the high and low MCM6 expression groups,along with the predicted immunotherapeutic response using Tumor Immune Dysfunction And Exclusion(TIDE),to assess the role of MCM6 in the immune landscape associated with cervical cancer and the responsiveness of immunotherapy;CIBERSORT was used to calculate the degree of immune infiltration between the high and low MCM6 expression groups in cervical cancer data samples;KaplanMeier method,univariate and multifactorial Cox proportional risk models were applied to analyze the relationship between MCM6 gene expression and prognosis of cervical cancer patients;Gene Set Enrichment Analysis(GSEA)analysis was performed to find the enrichment pathways of MCM6 in different groups.Based on the single cell level,we analyzed the cell subpopulations in which MCM6 was mainly expressed,and explored the biological functions of T proliferation(T prolif)cells through GSEA analysis and cell communication analysis,and further explored the immune mechanism of MCM6 in the microenvironment of cervical cancer.The Kaplan-Meier method was applied to analyze the correlation between T prolif Gene Signature and overall survival(OS)of cervical cancer patients.Results In TCGA cervical cancer data,the expression of MCM6 levels in tumor tissues was significantly higher than in normal cervical tissues;MCM6 expression correlated with the stage of cervical cancer patients,etc.;high expression levels of MCM6 correlated with MMR gene,HRR gene and HRR Signature;there were significant differences in expression between high and low MCM6 expression groups in ICMs,and significant differences in immunotherapy response predicted by TIDE in high and low groups.GSEA analysis showed that the high MCM6 expression group mainly affected the prognosis of patients by regulating the cell cycle through DNA replication and repair,and was associated with higher infiltration of CD8+ T cells,T follicular helper(T fh)cells,and monocytes,and was positively correlated with OS;the low MCM6 expression group was associated with high infiltration of M0 macrophages,and the prognosis of patients was poor.In single-cell data,MCM6 was mainly highly expressed in T prolif cell subtype in the cervical cancer dataset and advanced basal cell carcinoma dataset,and the T prolif cell subpopulation in the MCM6 high expression group were mainly enriched for DNA replication and DNA strand extension,cell cycle,etc.T prolif cells may influence tumor progression through ANXA1/FPR1 and CXCL16/CXCR6 pathways.The prognosis of patients with high expression of T prolif Gene Signature was significantly better than that of low expression group.Conclusion MCM6 may be a potential clinical indicator to predict tumor progression,metastasis and prognosis in patients with cervical cancer. |