Immune Infiltration Characteristics and a Gene Prognostic Signature Associated With the Immune Infiltration in Head and Neck Squamous Cell Carcinoma.

Immune Infiltration Characteristics and a Gene Prognostic Signature Associated With the Immune Infiltration in Head and Neck Squamous Cell Carcinoma.
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DOI:
10.3389/fgene.2022.848841
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发表时间:
2022
影响因子:
3.7
通讯作者:
Zhou, Yunfeng
Zhou, Yunfeng
中科院分区:
生物学3区
文献类型:
--
作者:
Zhu, Chunmei;Wu, Qiuji;Yang, Ningning;Zheng, Zhewen;Zhou, Fuxiang;Zhou, Yunfeng

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背景资料:免疫治疗已成为复发性和转移性头颈部鳞状细胞癌(HNSCC)的新标准治疗,PD-L1是广泛使用的免疫应答生物标志物。然而,大多数癌症患者的PD-L1表达较低,用于筛选受益于免疫治疗的人群的替代生物标志物仍在探索中。肿瘤微环境(TME),特别是肿瘤免疫浸润细胞,调节机体免疫功能,影响肿瘤生长,有望成为免疫治疗的生物标志物。 目的:本文主要探讨免疫浸润细胞模式如何影响免疫功能,从而影响HNSCC患者的预后。 方法:根据HNSCC的转录组数据,采用CIBERSORT算法生成免疫浸润细胞谱。使用一致聚类来划分具有不同免疫细胞浸润模式的组。从高和低免疫细胞浸润(ICI)组获得的差异表达基因(DEG)进行Kaplan-Meier和单变量考克斯分析。采用多变量考克斯分析,构建预后特征时涉及显著的复发相关DEG。 结果:在我们的研究中,从高ICI和低ICI组中获得了408个DEG,其中59个与总生存率(OS)显著相关。逐步多变量考克斯分析建立了一个16个基因的预后标志,可以区分HNSCC患者的良好和不良预后。ROC曲线和列线图验证了预后标志的敏感性和准确性。1年、2年和3年的AUC值分别为0.712、0.703和0.700。TCGA-HNSCC队列、GSE 65858队列和独立的GSE 41613队列证明了类似的预后意义。值得注意的是,预后特征很好地区分了有希望的免疫抑制受体(IR)的表达,并可以预测对免疫治疗的反应。 结论:我们建立了一个基于肿瘤免疫细胞浸润(TICI)的16基因签名,它可以区分不同预后的患者,并帮助预测对免疫治疗的反应。
Background: Immunotherapy has become the new standard of care for recurrent and metastatic head and neck squamous cell carcinoma (HNSCC), and PD-L1 is a widely used biomarker for immunotherapeutic response. However, PD-L1 expression in most cancer patients is low, and alternative biomarkers used to screen the population benefiting from immunotherapy are still being explored. Tumor microenvironment (TME), especially tumor immune-infiltrating cells, regulates the body’s immunity, affects the tumor growth, and is expected to be a promising biomarker for immunotherapy. Purpose: This article mainly discussed how the immune-infiltrating cell patterns impacted immunity, thereby affecting HNSCC patients’ prognosis. Method: The immune-infiltrating cell profile was generated by the CIBERSORT algorithm based on the transcriptomic data of HNSCC. Consensus clustering was used to divide groups with different immune cell infiltration patterns. Differentially expressed genes (DEGs) obtained from the high and low immune cell infiltration (ICI) groups were subjected to Kaplan–Meier and univariate Cox analysis. Significant prognosis-related DEGs were involved in the construction of a prognostic signature using multivariate Cox analysis. Results: In our study, 408 DEGs were obtained from high- and low-ICI groups, and 59 of them were significantly associated with overall survival (OS). Stepwise multivariate Cox analysis developed a 16-gene prognostic signature, which could distinguish favorable and poor prognosis of HNSCC patients. An ROC curve and nomogram verified the sensitivity and accuracy of the prognostic signature. The AUC values for 1 year, 2 years, and 3 years were 0.712, 0.703, and 0.700, respectively. TCGA-HNSCC cohort, GSE65858 cohort, and an independent GSE41613 cohort proved a similar prognostic significance. Notably, the prognostic signature distinguished the expression of promising immune inhibitory receptors (IRs) well and could predict the response to immunotherapy. Conclusion: We established a tumor immune cell infiltration (TICI)-based 16-gene signature, which could distinguish patients with different prognosis and help predict the response to immunotherapy.
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