A ferroptosis-related lncRNA signature predicts prognosis in ovarian cancer patients

Abstract

Background: Ovarian cancer (OC) is a common gynecological malignant tumor with poor prognosis.Ferroptosis is an iron-dependent modality of regulated cell death. The purpose of this study was to determine the prognostic ability of ferroptosis-related long non-coding RNAs (lncRNAs) in OC patients and construct a ferroptosis-related lncRNA prognostic model. Methods: The Cancer Genome Atlas (TCGA) and FerrDb databases were used to collect RNA sequencing data of OC patients and ferroptosis-related genes, respectively. OC patients were randomly assigned to the training or testing set. Pearson correlation analysis was used to identify ferroptosis-related lncRNAs. Univariate Cox, Least Absolute Shrinkage and Selection Operator (LASSO), and multivariate regression analyses were performed in the training set to develop a predictive model. The model was validated in the testing set and entire set. Survival analysis, receiver operating characteristic curves, independent prognostic factor analysis, and correlation analysis with clinical features were performed to evaluate the predictive value of the model. A nomogram was established to predict the survivability of OC patients over 1, 3, and 5 years. The distribution of distinct groups was investigated using principal component analysis, and the underlying the biological functions were explored using gene set enrichment analysis. Results: Eleven ferroptosis-related lncRNAs were determined to establish the prognostic model. Patients in the high-risk group had poor prognosis compared with the low-risk group in the training, testing and entire sets. The area under the receiver operating characteristic curve corresponding to 1-, 3-, and 5-year survival were 0.731, 0.796, and 0.805 in the training set; 0.704, 0.597, and 0.655 in the testing set; and 0.715, 0.691, and 0.736, in the entire set, respectively. The risk score correlated with age and grade. The risk score was also an independent prognostic factor in OC. A nomogram with high C-index (0.68) was constructed. An intuitive observation of the principal component analysis revealed a distinction between high-and lowrisk groups, and gene set enrichment analysis indicated that cancer-related pathways were enriched in the high-risk group. Conclusions: The signature composed of 11 ferroptosis-related lncRNAs accurately predicted the prognosis of OC patients.

Induction mechanism of ferroptosis: A novel therapeutic target in lung disease

“…Regarding the common cell morphologies in ferroptosis that distinguish it from apoptosis, necrosis, and autophagy, during the process the size of the mitochondria decreases, the density of bilayer membranes increases, and the mitochondrial cristae decrease or disappear; however, the cell membrane remains intact, the size of nucleus is normal, and there is no evidence of nuclear concentration or chromatin marginalization (Peng et al, 2021). In terms of biochemistry, ferroptosis is mainly manifested by the exhaustion of glutathione (GSH), a decline in glutathione peroxidase 4 (GPX4) activity, and the inability of lipid peroxides to be metabolized through the GSH reduction reaction catalyzed by GPX4.…”

Identification of ACSL4 as a biomarker and contributor of ferroptosis in clear cell renal cell carcinoma

“…The process of ferroptosis is a novel kind of cell death that is reliant on iron and is linked to oxidative stress (10). Ferroptosis is often hallmarked by an accumulation of cytoplasmic and lipid ROS, a decrease in the volume of the mitochondria, an enhancement in the density of the mitochondrial membrane, the perforation or deletion of mitochondrial cristae, as well as the disintegration of the outer membrane of the mitochondria (19). Recently, it was established that ACSL4 serves as an important factor of ferroptosis by gene filtering utilizing Genome-Wide CRISPR as well as microarray assessment of anti-ferroptosis cell lines (20).…”

“…According to several research reports, ferroptosis has a very strong correlation with a variety of human disorders (6,7,19). There have only been a few studies done on ferroptosis in relation to ccRCC.…”

Current progress of ferroptosis study in ovarian cancer

“…As a rising star, ferroptosis provides a new idea for the research of various diseases and plays a significantly important role in the remarkable success of tumor treatment. In recent years, a large number of studies have screened reliable mRNAs and genes to predict the prognosis of ovarian cancer patients by means of bioinformatics (Feng et al, 2022), comprehensive clinical analysis (Peng et al, 2021), and construction of ferroptosis-related gene models (Yang L. et al, 2021;Chen et al, 2021;Ye et al, 2021;You et al, 2021;Yu et al, 2021;Wang H. et al, 2022;Zou et al, 2022). It provides preciously applicable suggestions for exploring the therapeutic targets and prognostic indicators related to ferroptosis in ovarian cancer.…”