The Role of Ferroptosis-Related Molecules and Significance of Ferroptosis Score in Cervical Cancer.

Abstract

Ferroptosis, a form of cell death driven by iron-dependent lipid peroxidation, may be a potential treatment for many cancers, including cervical cancer (CC). However, the regulation of long noncoding RNAs (lncRNAs) in the process of ferroptosis and whether ferroptosis inducers could increase the cytotoxicity of conventional chemotherapy drugs remain to be further elucidated. We analyzed the variation of 55 differentially ferroptosis-related genes (FRGs) and the influence of mutations in CC patients. The patients with CC were classified into two ferroptosis clusters by the non-negative matrix factorization (NMF) algorithm. The principal components analysis (PCA) was used to measure the ferroptosis score (FerroScore) in patients with CC. Besides, FerroScore was used to predict the sensitivity of chemotherapy and responses to immunotherapy in patients with CC. Finally, experiments were performed to verify the regulatory effect of AC026790.1 on erastin-induced ferroptosis, as well as the effect of erastin in combination with cisplatin on the toxicity of CC cells (SiHa, HeLa). There were significant differences in the overall survival and immune cell infiltration between the two ferroptosis clusters. Patients with low FerroScore were more sensitive to chemotherapy drugs such as cisplatin and docetaxel. The low-FerroScore group had higher CD8+ T cell infiltration and immune checkpoint expression, demonstrating that patients with lower FerroScores were more sensitive to immunotherapy, which was consistent with the result of the submap method. In vitro, overexpression of AC026790.1 could promote erastin-induced ferroptosis, and the combination of erastin and cisplatin could increase the toxicity of CC cells. FerroScore has a potential prognostic value for CC that may provide a reference for chemotherapy and immunotherapy. LncRNA AC026790.1 can influence ferroptosis, and the combination of ferroptosis inducers and chemotherapy drugs can provide a new perspective on cancer treatment.