NOTCH gene pattern predicts prognosis, immune infiltration, and drug response in Head and Neck squamous cell carcinoma

IF 2 3区医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Stomatology Oral and Maxillofacial Surgery Pub Date : 2025-09-27 DOI:10.1016/j.jormas.2025.102582

Shanliang Ye , Lin Huang , Liyu Ma , Lingli Xu , Liehui Liu , Jiezhuang Li , Yufang Zhang , Baojuan Gao , Yuran Ji , Zhongwen Zheng , Hanguo Guo

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Abstract

Background

Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive cancer with poor prognosis. Although NOTCH signaling is frequently inactivated in HNSCC, the prognostic significance of NOTCH-related genes and their link to the tumor microenvironment remain unclear.

Methods

NOTCH-related genes were identified in HNSCC patients through univariate Cox regression and differential expression analyses. A prognostic risk model (NOTCH score) was constructed using LASSO regression. The association between the NOTCH score and clinical outcomes, immune infiltration, therapy response sensitivity was comprehensively evaluated. Single-cell RNA sequencing and immunohistochemistry were used to assess the cellular and tissue distribution of risk genes.

Results

Seven candidate genes (COL28A1, EFEMP1, FGF9, FMOD, ITGA5, ROBO1, and THBS1) were selected to construct the NOTCH-based prognostic model. Patients were stratified into high- and low-risk groups based on the median NOTCH score. High-risk patients exhibited significantly worse survival compared to the low-risk group. ROC analysis demonstrated robust prognostic performance, with AUC values exceeding 0.7 for 3-year survival in both training and validation cohorts. High NOTCH scores were associated with an immunosuppressive tumor microenvironment and poor response to immunotherapy. Drug sensitivity analysis revealed that high-risk patients were more sensitive to agents such as CMK, Parthenolide, and Thapsigargin. At both the single-cell and protein levels, the seven genes were predominantly expressed in fibroblasts and endothelial cells, suggesting their potential involvement in tumor stromal remodeling and microenvironment regulation.

Conclusion

We developed and validated a NOTCH-based prognostic model with strong predictive power in HNSCC. The NOTCH score may help assess immune status, predict treatment response, and guide personalized therapy.

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NOTCH基因模式预测头颈部鳞状细胞癌的预后、免疫浸润和药物反应。

背景：头颈部鳞状细胞癌（HNSCC）是一种侵袭性强、预后差的肿瘤。尽管NOTCH信号在HNSCC中经常失活，但NOTCH相关基因的预后意义及其与肿瘤微环境的联系尚不清楚。方法：通过单因素Cox回归和差异表达分析，鉴定HNSCC患者的notch相关基因。采用LASSO回归建立预后风险模型（NOTCH评分）。综合评价NOTCH评分与临床转归、免疫浸润、治疗反应敏感性的关系。单细胞RNA测序和免疫组织化学用于评估风险基因的细胞和组织分布。结果：选择7个候选基因（COL28A1、EFEMP1、FGF9、FMOD、ITGA5、ROBO1和THBS1）构建基于notch的预后模型。根据NOTCH中位评分将患者分为高危组和低危组。与低危组相比，高危组患者的生存率明显较差。ROC分析显示了良好的预后表现，在训练和验证队列中，3年生存率的AUC值均超过0.7。高NOTCH评分与免疫抑制肿瘤微环境和免疫治疗反应差相关。药物敏感性分析显示高危患者对CMK、Parthenolide、Thapsigargin等药物更为敏感。在单细胞和蛋白水平上，这7个基因主要在成纤维细胞和内皮细胞中表达，表明它们可能参与肿瘤基质重塑和微环境调节。结论：我们建立并验证了基于notch的HNSCC预后模型，该模型对HNSCC具有很强的预测能力。NOTCH评分可以帮助评估免疫状态，预测治疗反应，并指导个性化治疗。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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