A Neutrophil Extracellular Traps Signature Predicts the Clinical Outcomes and Immunotherapy Response in Head and Neck Squamous Cell Carcinoma.
A Neutrophil Extracellular Traps Signature Predicts the Clinical Outcomes and Immunotherapy Response in Head and Neck Squamous Cell Carcinoma.
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中性粒细胞胞外陷阱特征可预测头颈鳞状细胞癌的临床结果和免疫治疗反应
DOI：
10.3389/fmolb.2022.833771
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发表时间：
2022
影响因子：
5
通讯作者：
Cui J
中科院分区：
文献类型：
--
作者：
Chen N;He D;Cui J
背景：神经细胞外陷阱（NETs）在肿瘤的发生、转移和免疫逃逸中起重要作用。本研究旨在探讨NET相关基因在头颈部鳞状细胞癌（HNSCC）中的表达、临床预后价值及其与免疫治疗和抗癌药物的相关性。 方法：基于多个公共数据库，筛选HNSCC中差异表达的NET相关基因。为提高临床实用性和避免过拟合，采用单变量最小绝对收缩选择算子（LASSO）和多变量考克斯算法构建预后风险模型。进一步用列线图探讨该模型的临床应用价值。对模型进行了内部和外部验证。进一步探讨不同预后风险的HNSCC患者的免疫微环境、免疫表型评分（IPS）及抗癌药物敏感性。 结果：筛选出6个NET相关基因，构建了风险模型。在训练队列中，Kaplan-Meier（K-M）分析显示，低危HNSCC患者的总生存期（OS）显著优于高危HNSCC患者（p < 0.001）。诺模图还显示了较好的预后价值，C指数（0.726 vs 0.640）和曲线下面积（AUC）（3年时0.743 vs 0.706，5年时0.743 vs 0.645）优于先前的研究。校正图和决策曲线分析（DCA）也显示了令人满意的诺模图的预测能力。内部和外部验证进一步加强了临床预后模型的可信度。高风险组的肿瘤突变负荷（TMB）水平显著高于低风险组（p = 0.017），且TMB与风险评分呈正相关（R = 0.11; p = 0.019）。不同危险度HNSCC患者的免疫浸润差异有统计学意义（p < 0.05）。此外，IPS分析表明，抗PD-1（p < 0.001）、抗CTLA 4（p < 0.001）或联合免疫治疗（p < 0.001）对低风险HNSCC患者更有益。对抗癌药物的反应也与NET相关基因的表达密切相关（p < 0.001）。 结论：本研究确定了一种新的预后模型，可能有利于HNSCC患者的个性化治疗。
Background: Neutrophil extracellular traps (NETs) play an important role in the occurrence, metastasis and immune escape of cancers. This study aimed to investigate NET-related genes, their clinical prognostic value and their correlation with immunotherapy and anticancer drugs in patients with head and neck squamous cell carcinoma (HNSCC). Methods: Differentially expressed NET-related genes in HNSCC were identified based on multiple public databases. To improve the clinical practicability and avoid overfitting, univariable, least absolute shrinkage and selection operator (LASSO) and multivariable Cox algorithms were used to construct a prognostic risk model. A nomogram was further used to explore the clinical value of the model. Internal and external validation were conducted to test the model. Furthermore, the immune microenvironment, immunophenoscore (IPS) and sensitivity to anticancer drugs in HNSCC patients with different prognostic risks were explored. Results: Six NET-related genes were screened to construct the risk model. In the training cohort, Kaplan–Meier (K-M) analysis showed that the overall survival (OS) of low-risk HNSCC patients was significantly better than that of high-risk HNSCC patients (p < 0.001). The nomogram also showed a promising prognostic value with a better C-index (0.726 vs 0.640) and area under the curve (AUC) (0.743 vs 0.706 at 3 years, 0.743 vs 0.645 at 5 years) than those in previous studies. Calibration plots and decision curve analysis (DCA) also showed the satisfactory predictive capacity of the nomogram. Internal and external validation further strengthened the credibility of the clinical prognostic model. The level of tumor mutational burden (TMB) in the high-risk group was significantly higher than that in the low-risk group (p = 0.017), and the TMB was positively correlated with the risk score (R = 0.11; p = 0.019). Moreover, the difference in immune infiltration was significant in HNSCC patients with different risks (p < 0.05). Furthermore, the IPS analysis indicated that anti-PD-1 (p < 0.001), anti-CTLA4 (p < 0.001) or combining immunotherapies (p < 0.001) were more beneficial for low-risk HNSCC patients. The response to anticancer drugs was also closely correlated with the expression of NET-related genes (p < 0.001). Conclusion: This study identified a novel prognostic model that might be beneficial to develop personalized treatment for HNSCC patients.
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影响因子：
7.9
作者：
Jiao X;Wei X;Li S;Liu C;Chen H;Gong J;Li J;Zhang X;Wang X;Peng Z;Qi C;Wang Z;Wang Y;Wang Y;Zhuo N;Zhang H;Lu Z;Shen L
通讯作者：
Shen L
影响因子：
5.3
作者：
Dwyer M;Shan Q;D'Ortona S;Maurer R;Mitchell R;Olesen H;Thiel S;Huebner J;Gadjeva M
通讯作者：
Gadjeva M
影响因子：
5.2
作者：
Demkow U
通讯作者：
Demkow U
术后腹腔中的低密度中性粒细胞（LDN）通过产生中性粒细胞胞外捕获物（NET）来帮助腹膜复发。
影响因子：
4.6
作者：
Kanamaru R;Ohzawa H;Miyato H;Matsumoto S;Haruta H;Kurashina K;Saito S;Hosoya Y;Yamaguchi H;Yamashita H;Seto Y;Lefor AK;Sata N;Kitayama J
通讯作者：
Kitayama J
影响因子：
20.3
作者：
Laszik, Z;Jansen, PJ;Moore, KL
通讯作者：
Moore, KL