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中国癌症防治杂志

中国癌症防治杂志 ›› 2025, Vol. 17 ›› Issue (3): 372-382.doi: 10.3969/j.issn.1674-5671.2025.03.16

• 头颈部肿瘤专栏 • 上一篇    下一篇

整合生物信息学与细胞实验揭示CCR7和CTTN在头颈部鳞状细胞癌放疗应答中的作用 

  

  1. 广西医科大学附属肿瘤医院实验研究部；区域性高发肿瘤早期防治研究教育部重点实验室（广西医科大学）；广西医科大学生命科学研究院；南华大学附属第一医院肿瘤科；广西医科大学附属肿瘤医院头颈外科；广西医科大学国际教育学院
  • 出版日期:2025-06-25 发布日期:2025-07-10
  • 通讯作者: 谢莹 E-mail:xieying@gxmu.edu.cn
  • 基金资助:
    国家自然科学基金项目（82160386）；广西科技基地和人才专项（桂科AD25069077）；广西自然科学基金项目（2024GXNSFDA010032;2023GXNSFAA026189）

Integrating bioinformatics and cellular experiments to reveal the roles of CCR7 and CTTN in head and neck squamous cell carcinoma radiotherapy response 

  • Online:2025-06-25 Published:2025-07-10

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摘要： 目的 筛选头颈部鳞状细胞癌（head and neck squamous cell carcinoma, HNSCC）对放疗应答相关的潜在关键基因，并验证其功能。 方法 利用GSE39366数据集筛选放疗应答组与无应答组的差异表达基因（differentially expressed genes,DEGs）。通过癌症基因组图谱（the cancer genome atlas,TCGA）中的Cox比例风险回归分析，选择预后相关基因。通过韦恩图分析确定关键基因，并进行功能富集分析。评估关键基因的免疫微环境，包括ESTIMATE评分和免疫细胞浸润分析，以及它们与免疫相关基因的相互作用。通过整合关键基因与患者临床特征构建一个预后预测模型。使用外部数据集GSE41613验证关键基因的预后意义，使用CCK⁃8法和流式细胞术比较不同基因表达水平的细胞在放疗敏感性上的差异。通过RT⁃qPCR检测不同放疗剂量下关键基因表达的变化。结果 共筛选出519个DEGs和81个预后相关基因，确定CCR7、MS4A1、TBC1D10C和CTTN为HNSCC放疗敏感的关键基因。这些基因与肿瘤免疫浸润显著相关，基于这些基因构建的列线图模型表现出较好的预测能力。外部数据集验证表明，CCR7和CTTN与患者预后显著相关（均P<0.05），而MS4A1和TBC1D10C则未显示出显著的预后预测价值(均P>0.05)。体外实验进一步证实，CCR7表达升高且CTTN表达降低的HNSCC细胞对放疗的敏感性增加。CCR7和CTTN的表达水平随放疗剂量的变化而动态改变。 结论 CCR7和CTTN的表达水平与HNSCC的放疗敏感性及预后密切相关，其机制可能涉及免疫微环境调控。CCR7和CTTN有望成为HNSCC放疗敏感性预测的生物标志物和潜在治疗靶点。

关键词: 头颈鳞状细胞癌, 放疗敏感性, 预后, 免疫细胞浸润, 生物标志物

Abstract: Objective To identify potential key genes associated with radiotherapy response in head and neck squamous cell carcinoma (HNSCC) and validate their functional. Methods Differentially expressed genes (DEGs) between the radiotherapy response group and the non⁃response group were screened using the GSE39366 dataset. Prognostically relevant genes were selected through Cox proportional hazards regression analysis within the cancer genome atlas (TCGA). The key genes were identified through a Venn diagram analysis, followed by functional enrichment analysis. The immune microenvironment, including the ESTIMATE score and immune cell infiltration analysis, as well as interactions with immune⁃related genes, were performed on these key genes. A prognostic prediction model was developed by integrating these key genes with the clinical characteristics of patients. The prognostic impact of the key genes was validated using the external dataset GSE41613. Differences in radiosensitivity among cells with varying levels of gene expression were assessed via CCK⁃8 assays and flow cytometry. Changes in the expression of key genes under different radiotherapy doses were detected by RT⁃qPCR. Results A total of 519 DEGs and 81 prognostic⁃related genes were identified, with CCR7, MS4A1, TBC1D10C and CTTN being determined as key genes influencing radiosensitivity in HNSCC. These genes exhibited significant correlations with tumor immune infiltration, and the nomogram model constructed based on them demonstrated good predictive performance. External dataset validation indicated that CCR7 and CTTN were significantly associated with patient prognosis (all P<0.05), whereas MS4A1 and TBC1D10C did not show significant prognostic value (all P>0.05). In vitro experiments further confirmed that HNSCC cells with elevated CCR7 expression and reduced CTTN expression exhibited increased sensitive to radiotherapy. The expression levels of CCR7 and CTTN were observed to change dynamically with varying radiotherapy doses.  Conclusions The expression levels of CCR7 and CTTN are closely related to radiosensitivity and prognosis in HNSCC, potentially throungh mechanisms involving the regulation of immune microenvironment. CRRT and CTTN may serve as predictive biomarkers for HNSCC radiosensitivity and potential therapeutic targets.

Key words: Head and neck squamous cell carcinoma, Radiosensitivity, Prognosis, Immune cell infiltration, Biomarker

中图分类号: 

  • R739.91