Background: Cervical cancer (CC) is a common cancer in female, which is associated with problems like poor prognosis. Circular RNA (circRNA) is a kind of competing endogenous RNA (ceRNA) that has an important role in regulating microRNA (miRNA) in many cancers. The regulatory mechanisms of CC immune microenvironment and the transcriptome level remain to be fully explored. Methods: In this study, we constructed the ceRNA network through the interaction data and expression matrix of circRNA, miRNA and mRNA. Meanwhile, based on the gene expression matrix, CIBERSORT algorithm was used to reveal contents of tumor-infiltrating immune cells (TIICs). Then, we screened prognostic markers based on ceRNA network and immune infiltration and constructed two nomograms. In order to find immunological differences between the high- and low-risk CC samples, we examined multiple immune checkpoints and predicted the effect of PD-L1 ICI immunotherapy. In addition, the sensitive therapeutics for high-risk patients were screened, and the potential agents with anti-CC activity were predicted by Connective Map (CMap). Results: We mapped a ceRNA network including 5 circRNAs, 17 miRNAs and 129 mRNAs. From the mRNA nodes of the network six genes and two kind of cells were identified as prognostic makers for CC. Among them, there was a significant positive correlation between CD8+ T cells and SNX10 gene. The results of TIDE and single sample GSEA (ssGSEA) showed that T cells CD8 do play a key role in inhibiting tumor progression. Further, our study screened 24 drugs that were more sensitive to high-risk CC patients and several potential therapeutic agents for reference. Conclusions: Our study identified several circRNA-miRNA-mRNA regulatory axes and six prognostic genes based on the ceRNA network. In addition, through TIIC, survival analysis and a series of immunological analyses, T cells were proved to be good prognostic markers, besides play an important role in the immune process. Finally, we screened 24 potentially more effective drugs and multiple potential drug compounds for high- and low-risk patients.
Cervical cancer (CC) is a common cancer among women with poor prognosis. Circular RNA (circRNA), as a ceRNA, plays an important role in regulating microRNAs (miRNAs) in many cancers. The immune microenvironment of CC and the regulatory mechanisms at the transcriptomic level have not been fully explored. This study integrated the expression data of circRNA, Long non-coding RNA (lncRNA), miRNA and mRNA from TCGA database, GTEx database and GEO database, and mapped the ceRNA network through variation analysis and correlation analysis. Based on ceRNA network and tumor immune cell infiltration, we constructed two nomograms that can predict CC patients. Through co expression analysis and gene function enrichment, we explored the relationship between prognostic genes and immune cells in the model and the overall function of network node genes. In addition, we screened the drug RO-3306 with sensitivity to high-risk patients and predicted potential drugs with anti CC function by CMap. In conclusion, the research provides relevant information about the diagnosis, treatment and prognosis of CC patients, and several related drugs for reference. Prospective studies are necessary to validate the prognostic ability of this model.
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