CircRNA-Based Cervical Cancer Prognosis Model, Immunological Validation and Drug Prediction

Abstract

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.

Circular RNAs and cervical cancer: friends or foes? A landscape on circRNA-mediated regulation of key signaling pathways involved in the onset and progression of HPV-related cervical neoplasms

“…CircRNAs not only control the cell proliferation, migration, invasion, and metastasis of CC cells through modulating diverse signaling mechanisms but also have the ability of predicting the overall survival (OS) rate of patients with recurrence (Fig. 3 ) [ 94 , 182 ]. Tissue overexpression of oncogenic circRNAs is in strong association with poor survival rates in patients, while tumor suppressor circRNAs overexpression is related to good prognosis and higher survival rates [ 39 ].…”

Hsa_circ_0010882 facilitates hepatocellular carcinoma progression by modulating M1/M2 macrophage polarization

“…Circular RNAs (circRNAs) play a nonnegligible role in the genesis and progression of a variety of tumours with potential clinical applications and can participate in the regulation of macrophage polarization. [7][8][9] CircRNAs are covalently linked to form a closed loop structure without 5′ and 3′ ends, with cell or tissue expression specificity. 10 Evidence suggests that circRNAs absorb miR-NAs through the "sponge adsorption" effect and interact with RNA-binding protein.…”