A Ferroptosis-Related Prognostic Signature Based on Antitumor Immunity and Tumor Protein p53 Mutation Exploration for Guiding Treatment in Patients With Head and Neck Squamous Cell Carcinoma.
A Ferroptosis-Related Prognostic Signature Based on Antitumor Immunity and Tumor Protein p53 Mutation Exploration for Guiding Treatment in Patients With Head and Neck Squamous Cell Carcinoma.
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DOI：
10.3389/fgene.2021.732211
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发表时间：
2021
影响因子：
3.7
通讯作者：
Liao L
中科院分区：
文献类型：
--
作者：
Fan X;Ou Y;Liu H;Zhan L;Zhu X;Cheng M;Li Q;Yin D;Liao L
背景：由于缺乏准确的生物标志物指导，头颈部鳞状细胞癌（HNSCC）的治疗一直不理想。铁凋亡在肿瘤抑制和患者治疗中起着重要作用。然而，肿瘤蛋白p53（TP 53）突变可能通过铁凋亡促进肿瘤进展。因此，挖掘HNSCC中与预后相关的差异表达铁蛋白尿相关基因（PR-DE-FRG），构建准确指导临床治疗的预后模型显得尤为重要。研究方法：首先，使用从癌症基因组图谱（TCGA）获得的HNSCC数据来鉴定用于筛选候选基因的PR-DE-FRG以构建预后模型。我们不仅采用多种方法验证模型预测预后的准确性，而且从免疫微环境和突变的角度探讨了铁凋亡在HNSCC发生发展中的作用。最后，我们探讨了预后模型与临床治疗的相关性，并绘制了高精度的诺模图来预测预后。结果：从29个PR-DE-FRG中选择了17个，构建了具有良好预测性能的预后模型。低危组患者的CD 8 + T细胞、滤泡辅助性T细胞、调节性T细胞、肥大细胞、T细胞共刺激和II型干扰素应答数量较多。在低风险组中观察到更高的肿瘤突变负荷（TMB），并与更好的预后相关。在TP 53突变组中发现了较高的风险评分，并且与较差的预后相关。风险评分与PD-L1等免疫检查点抑制剂（ICI）相关基因的表达和6种化疗药物的IC 50密切相关。我们建立的诺模图在预测预后方面有较好的效果。结论：铁凋亡可能通过免疫微环境和TP 53基因突变参与了HNSCC的发生发展。该模型可作为HNSCC患者免疫治疗和化疗效果及预后的有效预测指标。
Background: Due to the lack of accurate guidance of biomarkers, the treatment of head and neck squamous cell carcinoma (HNSCC) has not been ideal. Ferroptosis plays an important role in tumor suppression and treatment of patients. However, tumor protein p53 (TP53) mutation may promote tumor progression through ferroptosis. Therefore, it is particularly important to mine prognostic-related differentially expressed ferroptosis-related genes (PR-DE-FRGs) in HNSCC to construct a prognostic model for accurately guiding clinical treatment. Methods: First, the HNSCC data obtained from The Cancer Genome Atlas (TCGA) was used to identify PR-DE-FRGs for screening candidate genes to construct a prognostic model. We not only used a variety of methods to verify the accuracy of the model for predicting prognosis but also explored the role of ferroptosis in the development of HNSCC from the perspective of the immune microenvironment and mutation. Finally, we explored the correlation between the prognostic model and clinical treatment and drew a high-precision nomogram to predict the prognosis. Results: Seventeen of the 29 PR-DE-FRGs were selected to construct a prognostic model with good predictive performance. Patients in the low-risk group were found to have a greater number of CD8 + T cells, follicular helper T cells, regulatory T cells, mast cells, T-cell costimulations, and type II interferon responses. A higher tumor mutation burden (TMB) was observed in the low-risk group and was associated with a better prognosis. A higher risk score was found in the TP53 mutation group and was associated with a worse prognosis. The risk score is closely related to the expression of immune checkpoint inhibitors (ICIs)-related genes such as PD-L1 and the IC50 of six chemotherapeutic drugs. The nomogram we constructed performs well in predicting prognosis. Conclusion: Ferroptosis may participate in the progression of HNSCC through the immune microenvironment and TP53 mutation. The model we built can be used as an effective predictor of immunotherapy and chemotherapy effects and prognosis of HNSCC patients.
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T细胞共刺激和共抑制的分子机制。
DOI：
10.1038/nri3405
发表时间：
2013-04
期刊：
Nature reviews. Immunology
影响因子：
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DOI：
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期刊：
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