Prognostic Value of a Ferroptosis-Related Gene Signature in Patients With Head and Neck Squamous Cell Carcinoma.
Prognostic Value of a Ferroptosis-Related Gene Signature in Patients With Head and Neck Squamous Cell Carcinoma.
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DOI：
10.3389/fcell.2021.739011
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发表时间：
2021
影响因子：
5.5
通讯作者：
Huang W
中科院分区：
文献类型：
--
作者：
He D;Liao S;Xiao L;Cai L;You M;He L;Huang W
背景资料：铁凋亡是一种铁依赖的程序性细胞死亡（PCD）形式，在肿瘤发生中起着至关重要的作用，并可能影响放射治疗和免疫治疗的抗肿瘤效果。本研究旨在探讨头颈部鳞状细胞癌（HNSCC）患者中不同的铁凋亡相关基因，其预后价值及其与免疫治疗的关系。方法：基于多个公共数据库，筛选HNSCC中铁代谢相关基因的差异表达。为避免过拟合，提高临床实用性，采用单变量、最小绝对收缩选择算子（LASSO）和多变量考克斯算法构建预后风险模型。此外，还构建了一个诺模图来预测个体预后。比较不同病理类型HNSCC患者肿瘤突变负荷（TMB）、免疫浸润和免疫检查点基因的差异。首先用Pearson法分析药敏结果与模型的相关性。结果：筛选出10个与铁凋亡相关的基因，构建了预后风险模型。Kaplan-Meier（K-M）分析显示，高危组HNSCC患者的预后明显低于低危组（P < 0.001），且1年、3年和5年受试者工作特征（ROC）曲线的曲线下面积（AUC）逐年增加（0.665、0.743和0.755）。内外部验证进一步验证了模型的准确性。然后，基于可靠性模型建立诺模图。列线图的C指数（0.752 vs. 0.640）上级优于既往研究，AUC（1年时0.729 vs. 0.597，3年时0.828 vs. 0.706，5年时0.853 vs. 0.645）、校准图和决策曲线分析（DCA）也显示了令人满意的预测能力。HNSCC患者TMB与危险度评分呈正相关（R = 0.14; P < 0.01）。免疫浸润和免疫检查点基因差异有统计学意义（P < 0.05）。Pearson相关分析显示，模型与抗肿瘤药物敏感性之间有显著相关性（P < 0.05）。结论：我们的研究结果确定了潜在的新的治疗靶点，为HNSCC患者的个体化治疗提供了进一步的潜在改善。
Background: Ferroptosis is an iron-dependent programmed cell death (PCD) form that plays a crucial role in tumorigenesis and might affect the antitumor effect of radiotherapy and immunotherapy. This study aimed to investigate distinct ferroptosis-related genes, their prognostic value and their relationship with immunotherapy in patients with head and neck squamous cell carcinoma (HNSCC). Methods: The differentially expressed ferroptosis-related genes in HNSCC were filtered based on multiple public databases. To avoid overfitting and improve clinical practicability, univariable, least absolute shrinkage and selection operator (LASSO) and multivariable Cox algorithms were performed to construct a prognostic risk model. Moreover, a nomogram was constructed to forecast individual prognosis. The differences in tumor mutational burden (TMB), immune infiltration and immune checkpoint genes in HNSCC patients with different prognoses were investigated. The correlation between drug sensitivity and the model was firstly analyzed by the Pearson method. Results: Ten genes related to ferroptosis were screened to construct the prognostic risk model. Kaplan-Meier (K-M) analysis showed that the prognosis of HNSCC patients in the high-risk group was significantly lower than that in the low-risk group (P < 0.001), and the area under the curve (AUC) of the 1-, 3- and 5-year receiver operating characteristic (ROC) curve increased year by year (0.665, 0.743, and 0.755). The internal and external validation further verified the accuracy of the model. Then, a nomogram was build based on the reliable model. The C-index of the nomogram was superior to a previous study (0.752 vs. 0.640), and the AUC (0.729 vs. 0.597 at 1 year, 0.828 vs. 0.706 at 3 years and 0.853 vs. 0.645 at 5 years), calibration plot and decision curve analysis (DCA) also shown the satisfactory predictive capacity. Furthermore, the TMB was revealed to be positively correlated with the risk score in HNSCC patients (R = 0.14; P < 0.01). The differences in immune infiltration and immune checkpoint genes were significant (P < 0.05). Pearson analysis showed that the relationship between the model and the sensitivity to antitumor drugs was significant (P < 0.05). Conclusion: Our findings identified potential novel therapeutic targets, providing further potential improvement in the individualized treatment of patients with HNSCC.
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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：
28.2
作者：
Erkes, Dan A.;Cai, Weijia;Aplin, Andrew E.
通讯作者：
Aplin, Andrew E.
影响因子：
10.9
作者：
Efimova I;Catanzaro E;Van der Meeren L;Turubanova VD;Hammad H;Mishchenko TA;Vedunova MV;Fimognari C;Bachert C;Coppieters F;Lefever S;Skirtach AG;Krysko O;Krysko DV
通讯作者：
Krysko DV
影响因子：
13.8
作者：
Bogdan AR;Miyazawa M;Hashimoto K;Tsuji Y
通讯作者：
Tsuji Y
影响因子：
4.7
作者：
Liu B;Su Q;Ma J;Chen C;Wang L;Che F;Heng X
通讯作者：
Heng X