Abstract: Objective    To explore the expression patterns of chemokine receptor C-X-C motif chemokine receptor 7（CXCR7）and its ligands，C-X-C motif chemokine ligand（CXCL）11 and CXCL12，in the tumor microenvironment of head and neck squamous cell carcinoma（HNSCC）as well as the correlation between the expression of CXCR7 and NIMA-related kinase 1（NEK1）. Methods    The expression patterns of CXCR7，CXCL11，and CXCL12 in different cell types within the HNSCC tumor microenvironment were analyzed by GO analysis and UMAP visualization of GSE103322 data set from gene expression omnibus. Kaplan-Meier survival curve was drawn using the RNA-seq data set from Kaplan-Meier Plotter database to assess the influence of CXCR7 expression level on the prognosis of HNSCC patients. The tumor and tumor adjacent normal tissues were obtained from 34 HSNCC patients（excluding nasopharyngeal carcinoma）in Department of Stomatology，Sijing Hospital，Songjiang District，Shanghai, from January to September 2024. The expression of CXCR7 and NEK1 in tissues was examined under microscopy after immunohistochemical staining. Results   In the HNSCC tumor microenvironment，CXCR7 was mainly expressed in fibroblasts，malignant cells，and endothelial cells. CXCL11 was only expressed in some malignant cells，while CXCL12 was mainly expressed in fibroblasts. The survival rate of the CXCR7 low-expression group was higher than that of the CXCR7 high-expression group（HR = 1.69，95%CI：1.24-2.29，P < 0.001）. Immunohistochemistry showed that CXCR7 was mainly expressed in the cell membrane，while NEK1 was mainly expressed in the cytoplasm. The high-expression rate of CXCR7 and NEK1 in HNSCC tumor tissues was higher than that in their adjacent normal tissues（χ2 values were 15.942 and 10.692，respectively，P < 0.05 for both）. The expression score of CXCR7 was positively correlated with that of NEK1 in HNSCC tumor tissues（r = 0.802，P < 0.001）. Conclusion    CXCR7 may be an important biological marker for prognosis of HNSCC. CXCR7 and its ligands may play critical roles in regulating immune infiltration and function in the HNSCC tumor microenvironment. CXCR7 and NEK1 may synergistically promote HNSCC progression. However，the detailed regulatory mechanisms of them still need to be elucidated.

Key words: C-X-C motif chemokine receptor 7, C-X-C motif chemokine ligand, NIMA-related kinase 1, head and neck squamous cell carcinoma, tumor microenvironment, biological feature

摘要： 目的    研究CXC趋化因子受体7（C-X-C motif chemokine receptor 7，CXCR7）、CXC趋化因子配体（C-X-C motif chemokine ligand，CXCL）11和CXCL12在头颈部鳞状细胞癌（head and neck squamous cell carcinoma，HNSCC）肿瘤微环境中表达特征，以及CXCR7和NIMA相关激酶1（NIMA-related kinase 1，NEK1）在HNSCC组织中表达相关性。方法    利用基因表达数据库（gene expression omnibus，GEO）中GSE103322数据集进行GO聚类和UMAP可视化，分析CXCR7及其配体CXCL11和CXCL12在HNSCC肿瘤微环境不同类型细胞中的表达情况。利用Kaplan-Meier Plotter数据库中RNA-seq数据集绘制Kaplan-Meier生存曲线，分析CXCR7的表达对HNSCC预后的影响。选取2024年1—9月于上海市松江区泗泾医院口腔科就诊的HNSCC（鼻咽癌除外）患者34例，将术中获取的HNSCC癌组织和癌旁组织进行免疫组织化学染色，镜下观察并评价CXCR7和NEK1在HNSCC组织中表达情况。结果    在HNSCC肿瘤微环境中，CXCR7主要在成纤维细胞、恶性细胞和内皮细胞中表达，CXCL11仅在部分恶性细胞中表达，CXCL12主要在成纤维细胞中表达。CXCR7低表达组生存率高于CXCR7高表达组，差异有统计学意义（HR = 1.69，95%CI：1.24 ~ 2.29，P < 0.001）。免疫组织化学染色结果显示，CXCR7主要在细胞膜上表达，NEK1主要在细胞质内表达，CXCR7和NEK1在HNSCC癌组织中的高表达率均大于癌旁组织，差异有统计学意义（χ2值分别为15.942、10.692，均P < 0.05）；在HNSCC癌组织中CXCR7与NEK1的表达评分呈正相关（r = 0.802，P < 0.001）。结论    CXCR7可能是HNSCC预后相关的重要生物标志物，CXCR7及其配体在调控HNSCC肿瘤微环境中的免疫细胞浸润和功能方面可能发挥重要作用。CXCR7和NEK1可能协同促进HNSCC的发展，但二者作用机制仍需进一步探究。

关键词: CXC趋化因子受体7, CXC趋化因子配体, NIMA相关激酶1, 头颈部鳞状细胞癌, 肿瘤微环境, 生物学特征