A Novel Ferroptosis-Related lncRNA Signature and an Immune Perspective of Cervical Cancer

Abstract Background: Cervical cancer (CC) is the most common reproductive neoplasm in women, especially in developing countries. Ferroptosis, a novel type of cell death, and lncRNAs play critical roles in the prognosis of CC patients and antitumor immunity. Methods: A ferroptosis-related lncRNA signature (FRLS) was constructed by LASSO Cox regression analysis. Kaplan-Meier analysis, receiver operating characteristic (ROC) curve analysis, multivariate analysis, and nomogram were used to evaluate and predict the FRLS. Based on the FRLS, immune-related genes, the tumor microenvironment (TME), immune checkpoints, and immunotherapy were investigated. Results: The FRLS was composed of ten lncRNAs and was markedly associated with the overall survival (OS) of CC patients. Gene set enrichment analysis (GSEA) demonstrated that the FRLS was largely associated with immune-related pathways. Weighted gene co-expression network analysis (WGCNA) was performed to analyze immune-related genes and to identify the optimal modules and genes. TLR4 was eventually identified, and its expression was verified in the Gene Expression Omnibus (GEO) database. Then, quantitative real-time PCR (qRT-PCR) was used to validate the results in CC and paracancerous tissues. Besides, our results showed that CD8+ T cells were significantly correlated between the low- and high-risk groups, and it could modulate ferroptosis during tumor immunotherapy. The expression of immune checkpoints was substantially different between the two groups. Additionally, tumor immune dysfunction and exclusion (TIDE) was applied to predict the sensitivity of immune checkpoint inhibitor (ICI) treatment. Conclusion: The FRLS established was significantly associated with prognosis; moreover, the FRLS is a prospective therapeutic target, and combined with immunotherapy, can be used in the treatment of CC patients.