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免疫与铁死亡相关基因联合构建头颈部鳞状细胞癌新的预后模型

Immunization Combined with Ferroptosis Related Genes to Construct a New Prognostic Model for Head and Neck Squamous Cell Carcinoma.

作者信息

Yang Linhui, Chen Zhiwei, Liu Yunliang, Wang Xiaoyan, Li Jing, Ye Qing

机构信息

Department of Otolaryngology-Head and Neck Surgery, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou 350001, China.

The Graduate School, Fujian Medical University, Fuzhou 350001, China.

出版信息

Cancers (Basel). 2022 Aug 24;14(17):4099. doi: 10.3390/cancers14174099.

Abstract

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 CD8T 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.

摘要

铁死亡是一种新型的程序性细胞死亡,在多种肿瘤中起关键作用。此外,免疫与铁死亡密切相关。然而,在头颈部鳞状细胞癌(HNSC)的调控中,免疫-铁死亡相关mRNA(IFRMs)仍未被完全了解。本文旨在研究IFRMs对头颈部鳞状细胞癌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数据库和先前的数据中挖掘RNA测序和相关临床数据。在R软件中,使用“DESeq2”包分析IFRMs的差异表达。我们使用单变量Cox分析来判断IFRMs的预后。使用最小绝对收缩和选择算子(LASSO)和Cox回归,建立了12个IFRMs的预测模型。在本研究中,使用Kaplan-Meier生存曲线和受试者工作特征(ROC)曲线分析来评估预测结果。此外,还讨论了免疫景观、体细胞突变和药物敏感性等因素。我们成功构建了12个IFRMs的特征。根据该特征获得的风险评分将患者分为两个风险组。与传统的临床病理特征相比,基于特征的风险评分对头颈部鳞状细胞癌患者的生存更具预测性。此外,两组之间CD8T细胞和巨噬细胞M0的表达差异显著。此外,与低风险组相比,高风险组中TNFSF9和CD44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。接下来,高风险组对博舒替尼、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等化疗药物更敏感。最后,对这12个基因的关联和潜在价值进行了深入分析。总之,本文建立的12个IFRMs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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed92/9454905/f300b89b2693/cancers-14-04099-g001.jpg

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