Abstract
Both ferroptosis and lncRNAs are significant for ovarian cancer (OC). Whereas, the study of ferroptosis-related lncRNAs (FRLs) still few in ovarian cancer. We first constructed an FRL-signature for patients with OC in the study. A total of 548 FRLs were identified for univariate Cox regression analysis, and 21 FRLs with significant prognosis were identified. The prognostic characteristics of nine FRLs was constructed and validated, showing opposite prognosis in two subgroups based on risk scores. The multivariate Cox regression analysis and nomogram further verified the prognostic value of the risk model. By calculating ferroptosis score through ssGSEA, we found that patients with higher risk scores exhibited higher ferroptosis scores, and high ferroptosis score was a risk factor. There were 40 microenvironment cells with significant differences in the two groups, and the difference of Stromal score between the two groups was statistically significant. Six immune checkpoint genes were expressed at different levels in the two groups. In addition, five m6A regulators (FMR1, HNRNPC, METTL16, METTL3, and METTL5) were higher expressed in the low-risk group. GSEA revealed that the risk model was associated with tumor-related pathways and immune-associated pathway. We compared the sensitivity of chemotherapy drugs between the two risk groups. We also explored the co-expression, ceRNA relation, cis and trans interaction of ferroptosis-related genes and lncRNAs, providing a new idea for the regulatory mechanisms of FRLs. Moreover, the nine FRLs were selected for detecting their expression levels in OC cells and tissues.
Highlights
150,000 women die of ovarian cancer (OC) every year, making it the highest death rate among gynecological tumors (Lheureux et al, 2019)
The result showed that the identified Ferroptosis-related gene (FRG) were closely related to several important biological processes or pathways, such as cellular response to tumor necrosis factor (Figure 2C), response to hypoxia (Figure 2C), PI3K-Akt/ MAPK/HIF-1/p53 signaling pathway (Figure 2D), etc
548 ferroptosis-related lncRNA (FRL) were obtained by Pearson correlation analysis (|Pearson correlation coefficient (PCC)| >0.5, p < 0.001) and FRL with significant prognosis was mined (p < 0.05)
Summary
150,000 women die of ovarian cancer (OC) every year, making it the highest death rate among gynecological tumors (Lheureux et al, 2019). The development of OC is regulated by many cytokines and signaling pathways (Narod, 2016). The prognosis for early-stage cancer patients is better, the vast majority of patients are already in the advanced stage when they are first. Ferroptosis is a process that regulates cell death and its particularity is lipid peroxide in cell membrane in an irondependent manner, which is different from apoptosis and necrosis (Yang and Stockwell, 2008). Ferroptosis is correlated with a variety of biochemical processes and can inhibit the proliferation of tumor tissues by depriving iron in cancer cells or changing the metabolism of iron ions in tumor tissues (Mou et al, 2019; Xu et al, 2019; Wang et al, 2020a; Wu et al, 2020). Studies have shown that continuous iron stimulation is one of the high-risk factors for the occurrence and development of OC(Lattuada et al, 2015) and ferroptosis is considered as a potential therapeutic target for OC (Lin and Chi, 2020)
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