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NKAP:一种新型的m6A RNA结合蛋白可预测头颈部鳞状细胞癌的预后和免疫治疗反应。

NKAP: A new m6A RNA binding protein predicts prognosis and immunotherapy response in head and neck squamous cell carcinoma.

作者信息

Arumugam Paramasivam, Manicka Vasagam Jeevitha, Jayaseelan Vijayashree Priyadharsini

机构信息

Molecular Biology Lab, Centre for Cellular and Molecular Research, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University, Chennai, India.

Department of Periodontics, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University, Chennai, India.

出版信息

J Stomatol Oral Maxillofac Surg. 2025 Jun;126(3S):102265. doi: 10.1016/j.jormas.2025.102265. Epub 2025 Jan 25.

Abstract

OBJECTIVE

This study aimed to investigate whether NKAP (nuclear factor κB activating protein) serves as a prognostic marker and predictive biomarker for immunotherapy response in head and neck squamous cell carcinoma (HNSCC).

METHODS

A retrospective cohort study combined with in vitro analyses was conducted. NKAP mRNA expression levels were assessed in 520 HNSCC tumor tissues and 44 normal tissues from the TCGA dataset and validated in a clinical cohort (n = 32). Clinical correlations with overall survival and immunotherapy outcomes were analyzed. The key pathological variables included tumor stage, grade, HPV status, and TP53 mutation. Appropriate statistics were calculated at a significant level (P<0.05).

RESULTS

In this study, we have collected tissue samples from HNSCC patients (mean age: 52.65 ± 7.76; males 66%, females 34%). NKAP was upregulated in HNSCC tissues compared to adjacent normal tissues (P < 0.001). The high expression of NKAP correlated with advanced tumor stage, grade, and reduced survival (P < 0.05). High expression levels of NKAP were also associated with anti-PD-L1 therapy response (P < 0.05). Functional enrichment analysis revealed NKAP involvement in cell cycle regulation, mRNA processing, and chromatin remodeling pathways critical for cancer progression.

CONCLUSION

NKAP represents a promising prognostic marker and therapeutic target for immunotherapy in HNSCC. Prospective studies are warranted to confirm these findings.

摘要

目的

本研究旨在探讨核因子κB激活蛋白(NKAP)是否可作为头颈部鳞状细胞癌(HNSCC)免疫治疗反应的预后标志物和预测生物标志物。

方法

进行了一项回顾性队列研究并结合体外分析。从TCGA数据集中评估了520例HNSCC肿瘤组织和44例正常组织中的NKAP mRNA表达水平,并在一个临床队列(n = 32)中进行了验证。分析了与总生存期和免疫治疗结果的临床相关性。关键病理变量包括肿瘤分期、分级、人乳头瘤病毒(HPV)状态和TP53突变。在显著水平(P<0.05)下计算适当的统计数据。

结果

在本研究中,我们收集了HNSCC患者的组织样本(平均年龄:52.65±7.76;男性66%,女性34%)。与相邻正常组织相比,HNSCC组织中NKAP表达上调(P < 0.001)。NKAP的高表达与肿瘤晚期、分级及生存期缩短相关(P < 0.05)。NKAP的高表达水平还与抗程序性死亡配体1(PD-L1)治疗反应相关(P < 0.05)。功能富集分析显示NKAP参与对癌症进展至关重要的细胞周期调控、mRNA加工和染色质重塑途径。

结论

NKAP是HNSCC免疫治疗中一个有前景的预后标志物和治疗靶点。有必要进行前瞻性研究以证实这些发现。

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