Integrated Analysis of Ferroptosis-Related Biomarker Signatures to Improve the Diagnosis and Prognosis Prediction of Ovarian Cancer.
Integrated Analysis of Ferroptosis-Related Biomarker Signatures to Improve the Diagnosis and Prognosis Prediction of Ovarian Cancer.
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铁死亡相关生物标志物特征的综合分析可改善卵巢癌的诊断和预后预测
DOI：
10.3389/fcell.2021.807862
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发表时间：
2021
影响因子：
5.5
通讯作者：
Yi X
中科院分区：
文献类型：
--
作者：
Wang H;Cheng Q;Chang K;Bao L;Yi X
卵巢癌仍然是最致命的妇科恶性肿瘤。铁下垂是一种特殊形式的铁依赖的非凋亡性细胞死亡，在各种癌症中起着至关重要的作用。然而，人们对铁性下垂在卵巢癌中的作用知之甚少。在这里，我们通过分析来自癌症基因组图谱和基因表达总览数据库的转录数据，表征了卵巢癌中铁下垂相关基因的诊断、预后和治疗价值。可靠的10基因铁下垂标志(HIC1、ACSF2、MUC1等)对卵巢癌的诊断进行了鉴定。值得注意的是，我们构建并验证了一个新的预后信号，包括三个FRG：HIC1、LPCAT3和DUOX1。我们还进一步开发了基于这三个基因的风险评分模型，将卵巢癌患者分为两个风险组。功能分析显示，高危人群的免疫反应和免疫相关途径丰富。同时，两组肿瘤微环境明显不同，高危组M2巨噬细胞浸润较多，免疫检查点关键分子表达较高。低风险患者表现出更有利的免疫治疗和化疗反应。我们得出结论，铁性下垂和免疫之间的串扰可能导致高危人群中患者预后较差。特别是，HIC1在卵巢癌中既有诊断价值又有预后价值。体外实验表明，抑制HIC1可通过诱导铁下垂提高化疗药物和免疫治疗药物的药物敏感性。我们的发现为FRGS在卵巢癌患者的早期发现、预后预测和个体化治疗决策中的潜在作用提供了新的见解。
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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影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
影响因子：
4
作者：
Dixon SJ;Winter GE;Musavi LS;Lee ED;Snijder B;Rebsamen M;Superti-Furga G;Stockwell BR
通讯作者：
Stockwell BR
Th17诱导自体树突状细胞疫苗接种可促进卵巢癌患者的抗原特异性细胞和体液免疫。
影响因子：
16.6
作者：
Block MS;Dietz AB;Gustafson MP;Kalli KR;Erskine CL;Youssef B;Vijay GV;Allred JB;Pavelko KD;Strausbauch MA;Lin Y;Grudem ME;Jatoi A;Klampe CM;Wahner-Hendrickson AE;Weroha SJ;Glaser GE;Kumar A;Langstraat CL;Solseth ML;Deeds MC;Knutson KL;Cannon MJ
通讯作者：
Cannon MJ
影响因子：
9
作者：
Gagliardi, Mara;Cotella, Diego;Corazzari, Marco
通讯作者：
Corazzari, Marco
影响因子：
64.8
作者：
Jiang, Le;Kon, Ning;Li, Tongyuan;Wang, Shang-Jui;Su, Tao;Hibshoosh, Hanina;Baer, Richard;Gu, Wei
通讯作者：
Gu, Wei