Liu Peng, Yang Dunhui, Ma Ruixia
Second Clinical Medical College, Ningxia Medical University, Yinchuan, Ningxia, PR China.
Otolaryngology Department, The First People's Hospital of Yinchuan, Otolaryngology Head and Neck Surgery Hospital, Yinchuan, Ningxia, PR China.
Medicine (Baltimore). 2025 May 23;104(21):e42561. doi: 10.1097/MD.0000000000042561.
To evaluate the correlation between glucosamine-6-phosphate isomerase 1 (GNPDA1) expression and prognosis, immune infiltration, and immune evasion in head and neck squamous cell carcinoma (HNSCC). We analyzed the expression of GNPDA1 in HNSCC tissues and obtained RNA sequence data from the Cancer Genome Atlas (TCGA) database. Kaplan-Meier survival analysis evaluated the relationship between GNPDA1 expression and advanced tumor stage, TNM stage, grading, and gender. Co-expressed genes with GNPDA1 were identified using TCGA data and annotated through gene ontology and Kyoto encyclopedia of genes and genomes analyses. A protein-protein interaction network was constructed using the STRING database. Single-sample gene set enrichment analysis was conducted based on TCGA and TIMER 2.0 databases to assess the correlation between GNPDA1 and immune infiltration. In addition, the location of GNPDA1 in tumor cell and immune cell structures was identified by the tumor immune stromal cells helper database, and potential protein-interacting molecules of GNPDA1 were elucidated in the STRING database. Potential GNPDA1 gene functions were assessed using gene set enrichment analysis. Our results indicate that the expression of GNPDA1 is elevated in HNSCC tissues (P < .05). GNPDA1 expression was positively correlated with tumor malignancy (P < .05) and negatively correlated with patient prognosis (P < .05). There was a significant correlation between high expression of GNPDA1 and advanced tumor stage, N-stage, or G-grade, and it was associated with gender. High GNPDA1 expression was associated with increased infiltration of resting CD4+T cells, macrophages M1 and M2, resting natural killer cells, monocytes, eosinophils, and naïve B cells (P < .05). In contrast, low GNPDA1 expression was associated with increased infiltration of activated natural killer cells, neutrophils, activated mast cells, macrophages M0, plasma cells, activated dendritic cells, CD8+T cells, memory B cells, regulatory T cells (Tregs), and naïve CD4+T cells (P < .05). In addition, GNPDA1 was observed to be closely associated with various immune evasion-related genes in HNSCC. The results of this study suggest that GNPDA1 can serve as a potential prognostic marker and therapeutic target for HNSCC and may be a key gene mediating immune evasion in HNSCC.
为评估6-磷酸氨基葡萄糖异构酶1（GNPDA1）表达与头颈部鳞状细胞癌（HNSCC）预后、免疫浸润及免疫逃逸之间的相关性。我们分析了HNSCC组织中GNPDA1的表达，并从癌症基因组图谱（TCGA）数据库获取了RNA序列数据。Kaplan-Meier生存分析评估了GNPDA1表达与肿瘤晚期、TNM分期、分级及性别之间的关系。利用TCGA数据鉴定与GNPDA1共表达的基因，并通过基因本体论和京都基因与基因组百科全书分析进行注释。使用STRING数据库构建蛋白质-蛋白质相互作用网络。基于TCGA和TIMER 2.0数据库进行单样本基因集富集分析，以评估GNPDA1与免疫浸润之间的相关性。此外，通过肿瘤免疫基质细胞辅助数据库确定GNPDA1在肿瘤细胞和免疫细胞结构中的位置，并在STRING数据库中阐明GNPDA1潜在的蛋白质相互作用分子。使用基因集富集分析评估GNPDA1基因的潜在功能。我们的结果表明，GNPDA1在HNSCC组织中的表达升高（P < 0.05）。GNPDA1表达与肿瘤恶性程度呈正相关（P < 0.05），与患者预后呈负相关（P < 0.05）。GNPDA1高表达与肿瘤晚期、N分期或G分级之间存在显著相关性，且与性别有关。GNPDA1高表达与静息CD4+T细胞、M1和M2巨噬细胞、静息自然杀伤细胞、单核细胞、嗜酸性粒细胞及幼稚B细胞浸润增加相关（P < 0.05）。相反，GNPDA1低表达与活化自然杀伤细胞、中性粒细胞、活化肥大细胞、M0巨噬细胞、浆细胞、活化树突状细胞、CD8+T细胞、记忆B细胞、调节性T细胞（Tregs）及幼稚CD4+T细胞浸润增加相关（P < 0.05）。此外，观察到GNPDA1与HNSCC中各种免疫逃逸相关基因密切相关。本研究结果表明，GNPDA1可作为HNSCC潜在的预后标志物和治疗靶点，可能是介导HNSCC免疫逃逸的关键基因。
