The Immune-related ceRNA Network in Prognosis of Cervical Cancer.

BACKGROUND: Immunotherapy is gaining attention and it is being included as one of the treatment strategies for cancer patients. However, the molecular mechanisms of immune-related genes and their affinity for cervical cancer progression remain unclear. In this study, we have developed an immune-related competing endogenous RNA [ceRNA] network and assessed the tumour infiltrating immune cells towards the prognosis of cervical cancer.

METHODS: Differential RNA expression pattern between stages I and II-IV of cervical cancer patients from The Cancer Genome Atlas [TCGA] was analyzed. Immune-related ceRNA network based on the immune gene signatures were retrieved and their targets were predicted using miRwalk 3.0. CIBERSORT was employed to identify the immune cell types based on their respective transcripts. The prognostic significance of RNAs in the ceRNA network and immune cell subsets was analyzed.

RESULTS: Significant differences in 22 long non-coding RNAs [lncRNAs], 15 microRNAs [miRNAs], and 252 messenger RNAs [mRNAs] between stages I and II-IV of cervical cancer were observed. Further, we shortlisted the 49 immune-related mRNAs based on immune gene signature and predicted their target miRNAs and lncRNAs. A potential ceRNA network of 4 lncRNAs, 10 miRNAs, and 11 mRNAs had a strong correlation for prognosis. Out of 11 protein-coding immune mRNAs, IRF4 and AZGP1 had high degrees of interaction. In addition, the evaluation of immune cell subsets showed increased infiltration of M1 macrophages had better survival outcome.

CONCLUSIONS: We have identified an immune-related ceRNA network based on differentially expressed transcripts between stages I and II-IV which may help predict the prognosis of cervical cancer.