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基于自然杀伤细胞的特征:头颈部鳞状细胞癌的预后分析。

Natural killer cell-based signature: Prognostic analysis in head and neck squamous cell carcinoma.

机构信息

Department of Head and Neck Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Department of Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

出版信息

J Gene Med. 2024 Feb;26(2):e3671. doi: 10.1002/jgm.3671.

Abstract

BACKGROUND

Head and neck squamous cell carcinoma (HNSC) is a challenging cancer with significant clinical implications. Natural killer (NK) cells have emerged as important players in tumor immunosurveillance, yet their role and potential as prognostic biomarkers in HNSC remain unclear.

METHODS

Quantitative analysis using multiple algorithms identified FCRL1, KIR3DL2 and ZNF541 as molecules significantly associated with local NK cell infiltration and patient survival. A prognostic model based on these molecules demonstrated robust predictive performance.

RESULTS

Analysis of high- and low-risk patient groups revealed distinct differences in the tumor microenvironment, indicating an inhibitory immune microenvironment in high-risk patients. Notably, low-risk patients exhibited potential sensitivity to immunotherapy and showed favorable responses to specific drugs such as axitinib, methotrexate, rapamycin and vorinostat. NK cells, important effectors of the innate immune response, were found to play a crucial role in HNSC immunity. The present study provides valuable insights into the correlation between FCRL1, KIR3DL2, ZNF541 and NK cell infiltration, paving the way for future investigations into their roles in HNSC. Activation of NOTCH signaling, MYC targets, DNA repair, E2F targets, epithelial-mesenchymal transition, G2M checkpoint and mitotic spindle pathways in high-risk patients suggests their involvement in disease progression and poor prognosis.

CONCLUSIONS

The present study reveals the significance of NK cells in HNSC and their potential as prognostic biomarkers. The CFKZ score offers a promising approach for predicting patient outcomes and guiding personalized treatment decisions in HNSC. These findings contribute to our understanding of HNSC immunobiology and hold implications for precision medicine in HNSC management.

摘要

背景

头颈部鳞状细胞癌(HNSC)是一种具有重要临床意义的挑战性癌症。自然杀伤(NK)细胞已成为肿瘤免疫监视的重要参与者,但它们在 HNSC 中的作用和作为预后生物标志物的潜力仍不清楚。

方法

使用多种算法进行定量分析,确定 FCRL1、KIR3DL2 和 ZNF541 是与局部 NK 细胞浸润和患者生存显著相关的分子。基于这些分子的预后模型表现出强大的预测性能。

结果

高风险和低风险患者组的分析显示肿瘤微环境存在明显差异,表明高风险患者存在抑制性免疫微环境。值得注意的是,低风险患者表现出对免疫治疗的潜在敏感性,并对特定药物如阿昔替尼、甲氨蝶呤、雷帕霉素和伏立诺他表现出有利的反应。NK 细胞是先天免疫反应的重要效应器,在 HNSC 免疫中发挥着关键作用。本研究提供了 FCRL1、KIR3DL2 和 ZNF541 与 NK 细胞浸润之间相关性的有价值见解,为进一步研究它们在 HNSC 中的作用铺平了道路。NOTCH 信号通路、MYC 靶点、DNA 修复、E2F 靶点、上皮-间充质转化、G2M 检查点和有丝分裂纺锤体通路在高风险患者中的激活表明它们参与了疾病进展和预后不良。

结论

本研究揭示了 NK 细胞在 HNSC 中的重要性及其作为预后生物标志物的潜力。CFKZ 评分提供了一种有前途的方法,可以预测患者的结局,并指导 HNSC 中的个性化治疗决策。这些发现有助于我们理解 HNSC 免疫生物学,并为 HNSC 管理中的精准医学提供了启示。

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