Integrated Analysis of Ferroptosis-Related Biomarker Signatures to Improve the Diagnosis and Prognosis Prediction of Ovarian Cancer
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...
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.807862/full |
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| author | Huan Wang Huan Wang Huan Wang Qi Cheng Qi Cheng Kaikai Chang Kaikai Chang Lingjie Bao Lingjie Bao Xiaofang Yi Xiaofang Yi |
| author_facet | Huan Wang Huan Wang Huan Wang Qi Cheng Qi Cheng Kaikai Chang Kaikai Chang Lingjie Bao Lingjie Bao Xiaofang Yi Xiaofang Yi |
| author_sort | Huan Wang |
| collection | DOAJ |
| description | 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. In vitro experiments demonstrated that inhibition of HIC1 improved drug sensitivity of chemotherapy and immunotherapy agents by inducing ferroptosis. Our findings provide new insights into the potential role of FRGs in the early detection, prognostic prediction, and individualized treatment decision-making for ovarian cancer patients. |
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| language | English |
| last_indexed | 2024-12-24T01:37:32Z |
| publishDate | 2022-01-01 |
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| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-b9286952fc184a0ebc797ceb4b0908562022-12-21T17:22:09ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-01-01910.3389/fcell.2021.807862807862Integrated Analysis of Ferroptosis-Related Biomarker Signatures to Improve the Diagnosis and Prognosis Prediction of Ovarian CancerHuan Wang0Huan Wang1Huan Wang2Qi Cheng3Qi Cheng4Kaikai Chang5Kaikai Chang6Lingjie Bao7Lingjie Bao8Xiaofang Yi9Xiaofang Yi10Department of Gynecology, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai, ChinaDepartment of Gynecology, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, ChinaShanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, ChinaDepartment of Gynecology, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, ChinaDepartment of Gynecology, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, ChinaDepartment of Gynecology, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, ChinaDepartment of Gynecology, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, ChinaOvarian 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. In vitro experiments demonstrated that inhibition of HIC1 improved drug sensitivity of chemotherapy and immunotherapy agents by inducing ferroptosis. Our findings provide new insights into the potential role of FRGs in the early detection, prognostic prediction, and individualized treatment decision-making for ovarian cancer patients.https://www.frontiersin.org/articles/10.3389/fcell.2021.807862/fullovarian cancerferroptosis-related genesdiagnosisprognosisimmunotherapychemotherapy |
| spellingShingle | Huan Wang Huan Wang Huan Wang Qi Cheng Qi Cheng Kaikai Chang Kaikai Chang Lingjie Bao Lingjie Bao Xiaofang Yi Xiaofang Yi Integrated Analysis of Ferroptosis-Related Biomarker Signatures to Improve the Diagnosis and Prognosis Prediction of Ovarian Cancer Frontiers in Cell and Developmental Biology ovarian cancer ferroptosis-related genes diagnosis prognosis immunotherapy chemotherapy |
| title | Integrated Analysis of Ferroptosis-Related Biomarker Signatures to Improve the Diagnosis and Prognosis Prediction of Ovarian Cancer |
| title_full | Integrated Analysis of Ferroptosis-Related Biomarker Signatures to Improve the Diagnosis and Prognosis Prediction of Ovarian Cancer |
| title_fullStr | Integrated Analysis of Ferroptosis-Related Biomarker Signatures to Improve the Diagnosis and Prognosis Prediction of Ovarian Cancer |
| title_full_unstemmed | Integrated Analysis of Ferroptosis-Related Biomarker Signatures to Improve the Diagnosis and Prognosis Prediction of Ovarian Cancer |
| title_short | Integrated Analysis of Ferroptosis-Related Biomarker Signatures to Improve the Diagnosis and Prognosis Prediction of Ovarian Cancer |
| title_sort | integrated analysis of ferroptosis related biomarker signatures to improve the diagnosis and prognosis prediction of ovarian cancer |
| topic | ovarian cancer ferroptosis-related genes diagnosis prognosis immunotherapy chemotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.807862/full |
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