Immunization Combined with Ferroptosis Related Genes to Construct a New Prognostic Model for Head and Neck Squamous Cell Carcinoma.
Immunization Combined with Ferroptosis Related Genes to Construct a New Prognostic Model for Head and Neck Squamous Cell Carcinoma.
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免疫联合铁下垂相关基因构建头颈部鳞状细胞癌预后新模型。
作者：
免疫结合铁凋亡被认为是一种新的肿瘤治疗模式，其在头颈部鳞癌中的调控机制尚不清楚。本研究的目的是探讨免疫性铁凋亡基因在头颈部鳞状细胞癌中的分子生物学作用。成功构建了12个IFRM签名，并使用TCGA数据库和相关数据资源将其分为高风险组和低风险组。在头颈部鳞状细胞癌患者中，基于特征的风险评分比传统的临床病理学特征更能预测生存率。CD 8 +T细胞和巨噬细胞M0的表达在两组间有显著性差异。与低危组相比，高危组中TNFSF 9和CD 44的表达明显升高。接下来，我们发现高风险突变的比例高于低风险组。此外，高危组对某些化疗药物更敏感。最后对模型基因进行相关性分析。本研究开发的12-IFRM标记物在头颈部鳞状细胞癌的临床预后和治疗预后预测方面具有良好的应用前景。铁凋亡是一种新型的程序性细胞死亡，在多种肿瘤中起着关键作用。此外，免疫与铁凋亡密切相关。然而，免疫铁凋亡相关的mRNA（IFRMs）仍然没有完全理解的头部和颈部鳞状细胞癌（HNSC）的调控。本研究的目的是探讨IFRMs对HNSC的预测及其可能的分子生物学作用。从TCGA数据库、ImmPort数据库、GeneCards数据库、FerrDb数据库和先前数据中挖掘RNA-Seq和相关临床数据。在R软件中，使用“DESeq 2”软件包分析IFRMs的差异表达。采用单因素考克斯分析判断IFRM的预后。采用最小绝对收缩选择算子（LASSO）和考克斯回归，建立了12种IFRM的预测模型。本研究采用Kaplan-Meier生存曲线和受试者工作特征（ROC）曲线对预测结果进行评价。此外，还讨论了免疫景观，体细胞突变和药物敏感性等因素。我们成功地构造了12-IFRM的签名。这两个风险组根据该签名获得的风险评分进行分类。与传统的临床病理特征相比，基于特征的风险评分更能预测HNSC患者的生存率。CD 8 +T细胞和巨噬细胞M0的表达在两组间有显著性差异。此外，与低危组相比，高危组中TNFSF 9和CD 44的表达显著增加。然后，我们发现高风险突变的比例高于低风险组。其次，高危组对化疗药物如博舒替尼、多西他赛、厄洛替尼、吉非替尼、伊马替尼、拉帕替尼和索拉非尼更敏感。最后，对这12个基因的关联性和潜在价值进行了深入分析。综上所述，本文建立的12-IFRM特征具有良好的应用前景，可有效用于预测头颈部鳞状细胞癌的临床结局和治疗反应。
Immunity combined with ferroptosis is being considered as a new tumor treatment modality, and its regulation in head and neck squamous cell carcinoma is still unknown. The purpose of this study was to look into the potential molecular biological roles of immune ferroptosis genes in head and neck squamous cell carcinoma. The 12-IFRM signatures were successfully constructed and classified into high- and low-risk groups using the TCGA database and related data resources. In patients with head and neck squamous cell carcinoma, feature-based risk scores were more predictive of survival than traditional clinicopathological features. Furthermore, the expression of CD8+T cells and macrophage M0 differed significantly between the two groups. The expression of TNFSF9 and CD44 in the high-risk groups was significantly increased compared with the low-risk groups. Next, we found a higher proportion of high-risk mutations than in the low-risk group. In addition, the high-risk group was more sensitive to some chemotherapy drugs. Finally, we performed correlation analysis on the model genes. In this paper, the 12-IFRM signatures was developed with promising application prospects for predicting the clinical outcomes and treatment outcomes in head and neck squamous cell carcinoma. Ferroptosis is a new type of programmed cell death that plays a pivotal role in a variety of tumors. Moreover, immunity is closely related to ferroptosis. However, immune-ferroptosis-related mRNAs (IFRMs) are still not fully understood in the regulation of head and neck squamous cell carcinoma (HNSC). The purpose of this paper was to investigate the IFRMs prediction of HNSC and its possible molecular biological role. RNA-Seq and related clinical data were mined from the TCGA database, ImmPort database, GeneCards database, FerrDb database, and previous data. In R software, the “DESeq2” package was used to analyze the differential expression of IFRMs. We used univariate Cox analysis to judge the prognosis of the IFRMs. Using the least absolute shrinkage and selection operator (LASSO) and Cox regression, a prediction model for 12 IFRMs was established. In this study, the Kaplan–Meier survival curve and receiver operating characteristic (ROC) curve analysis were used to evaluate the prediction results. Moreover, factors such as immune landscape, somatic mutations, and drug susceptibility are also discussed. We successfully constructed the signature of 12-IFRMs. The two risk groups were classified according to the risk score obtained by this signature. Compared with conventional clinicopathological features, the characteristic-based risk score was more predictive of survival in patients with HNSC. Furthermore, the expression of CD8+T cells and macrophage M0 differed significantly between the two groups. Moreover, the expression of TNFSF9 and CD44 in high-risk groups was significantly increased compared with the low-risk groups. Then, we found a higher proportion of high-risk mutations than in the low-risk group. Next, the high-risk group was more sensitive to chemotherapy drugs such as bosutinib, docetaxel, erlotinib, gefitinib, imatinib, lapatinib, and sorafenib. Finally, an in-depth analysis of the association and potential value of the 12 genes was performed. In summary, the 12-IFRM signatures established in this paper had good application prospects and could be effectively used to predict the clinical outcome and treatment response of head and neck squamous cell carcinoma.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
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：
14.9
作者：
The Gene Ontology Consortium
通讯作者：
The Gene Ontology Consortium
影响因子：
7.9
作者：
Huang, Fuhao;Pang, Jinlong;Li, Xian
通讯作者：
Li, Xian
DOI：
10.1126/science.aaf1490
发表时间：
2016-03-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
McGranahan N;Furness AJ;Rosenthal R;Ramskov S;Lyngaa R;Saini SK;Jamal-Hanjani M;Wilson GA;Birkbak NJ;Hiley CT;Watkins TB;Shafi S;Murugaesu N;Mitter R;Akarca AU;Linares J;Marafioti T;Henry JY;Van Allen EM;Miao D;Schilling B;Schadendorf D;Garraway LA;Makarov V;Rizvi NA;Snyder A;Hellmann MD;Merghoub T;Wolchok JD;Shukla SA;Wu CJ;Peggs KS;Chan TA;Hadrup SR;Quezada SA;Swanton C
通讯作者：
Swanton C