Abstract
Ovarian cancer is a kind of gynecological malignancy with high mortality. Ferroptosis is a new type of iron-dependent cell death characterized by the formation of lipid peroxides and excessive accumulation of reactive oxygen species. Studies have shown that ferroptosis modulates tumor genesis, progression, and invasion, including ovarian cancer. Based on the mRNA expression data from TCGA, we construct a scoring system using consensus clustering analysis, univariate Cox regression analysis, and least absolute selection operator. Then, we systematically evaluate the relationship between score and clinical characteristics of ovarian cancer. The result from the prediction of biofunction pathways shows that score serves as an independent prognostic marker for ovarian cancer and affects tumor progression by modulating tumor metastasis. Moreover, immunocytes such as activated CD4 T cell, activated CD8 T cell, regulatory T cells, macrophage, and stromal cells, including adipocytes, epithelial cells, and fibroblast infiltrate more in the tumor microenvironment in a high-score group, indicating ferroptosis can also affect tumor immune landscape. Critically, four potentially sensitive drugs, including staurosporine, epothilone B, DMOG, and HG6-64-1 based on the scores, are predicted, and DMOG is recognized as a novel targeted drug for ovarian cancer. In general, we construct the scoring system based on ferroptosis-related genes that can predict the prognosis of ovarian cancer patients and propose that ferroptosis may affect ovarian cancer progression by mediating tumor metastasis and immune landscape. Novel drugs to target ovarian cancer are also predicted.
Highlights
Ovarian cancer is the most lethal malignancy among gynecological tumors, killing about 150,000 women each year [1]
Our results show that the infiltration of immune cells and stromal cells is more in the high-score group. e results of GO and KEGG enrichment analyses indicate that ferroptosis-related biological pathways like cell–cell adhesion mediated by integrin and regulation of extracellular matrix disassembly are activated in the high-score group
We observed an elevated trend in the expression of ferroptosis tolerance-related genes in cluster 2 (Figure 1(e)), suggesting that ferroptosis affects the prognosis of ovarian cancer
Summary
Ovarian cancer is the most lethal malignancy among gynecological tumors, killing about 150,000 women each year [1]. According to the statistical results of cancer incidence and mortality in the United States in 2020, ovarian cancer mortality ranked fifth in female cancer mortality and ranked first in gynecologic tumor mortality in North America [2]. Due to the lack of typical clinical symptoms in the early stage, 75% of ovarian cancer patients have reached the advanced stage when diagnosed, and 70%–80% of patients relapse after treatment [3]. Most of the patients with advanced ovarian cancer develop into relapse and multi-drug resistant stages [5]. Mesenchymal has the highest degree of malignancy, and its invasion ability is the strongest among these four subtypes [7]. The sample has more infiltrating stromal cells [7]
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