AUTHOR=Wang Huan , Cheng Qi , Chang Kaikai , Bao Lingjie , Yi Xiaofang TITLE=Integrated Analysis of Ferroptosis-Related Biomarker Signatures to Improve the Diagnosis and Prognosis Prediction of Ovarian Cancer JOURNAL=Frontiers in Cell and Developmental Biology VOLUME=9 YEAR=2022 URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.807862 DOI=10.3389/fcell.2021.807862 ISSN=2296-634X ABSTRACT=
Ovarian cancer remains the most lethal gynecological malignancy. Ferroptosis, a specialized form of iron-dependent, nonapoptotic cell death, plays a crucial role in various cancers. However, the contribution of ferroptosis to ovarian cancer is poorly understood. Here, we characterized the diagnostic, prognostic, and therapeutic value of ferroptosis-related genes in ovarian cancer by analyzing transcriptomic data from The Cancer Genome Atlas and Gene Expression Omnibus databases. A reliable 10-gene ferroptosis signature (HIC1, ACSF2, MUC1, etc.) for the diagnosis of ovarian cancer was identified. Notably, we constructed and validated a novel prognostic signature including three FRGs: HIC1, LPCAT3, and DUOX1. We also further developed a risk score model based on these three genes which divided ovarian cancer patients into two risk groups. Functional analysis revealed that immune response and immune-related pathways were enriched in the high-risk group. Meanwhile, the tumor microenvironment was distinct between the two groups, with more M2 Macrophage infiltration and higher expression of key immune checkpoint molecules in the high-risk group than in the other group. Low-risk patients exhibited more favorable immunotherapy and chemotherapy responses. We conclude that crosstalk between ferroptosis and immunity may contribute to the worse prognosis of patients in the high-risk group. In particular, HIC1 showed both diagnostic and prognostic value in ovarian cancer.