口腔医学研究

口腔医学研究 ›› 2026, Vol. 42 ›› Issue (6): 478-486.DOI: 10.13701/j.cnki.kqyxyj.2026.06.004

• 口腔颌面外科学研究 • 上一篇    下一篇

SERPINE2的泛癌分析及与头颈部鳞状细胞癌肿瘤微环境的关联分析

马纪源, 农晟, 潘军臣, 孙雅楠, 张佳莉*   

  1. 口颌系统重建与再生全国重点实验室,口腔生物医学教育部重点实验室,口腔医学湖北省重点实验室,武汉大学口腔医(学)院口腔病理科 湖北 武汉 430079
  • 收稿日期:2025-06-16 出版日期:2026-06-28 发布日期:2026-06-23
  • 通讯作者: *张佳莉,E-mail:jiali_zhang@whu.edu.cn
  • 作者简介:马纪源(1999~),男,河北邯郸人,硕士在读,主要从事口腔肿瘤基础研究。
  • 基金资助:
    国家自然科学基金(编号:82273201)

Pan-cancer Analysis of SERPINE2 and Its Association with Tumor Microenvironment in Head and Neck Squamous Cell Carcinoma

MA Jiyuan, NONG Sheng, PAN Junchen, SUN Yanan, ZHANG Jiali*   

  1. State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, Department of Oral Pathology, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China
  • Received:2025-06-16 Online:2026-06-28 Published:2026-06-23

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摘要： 目的:本研究旨在探讨丝氨酸蛋白酶抑制剂E类成员2(serpin family E member 2, SERPINE2)在泛癌中的表达模式、预后、肿瘤微环境及其与肿瘤淋巴结转移的相关性,并揭示其在头颈部鳞状细胞癌(head and neck squamous cell carcinoma,HNSC)中的潜在功能通路。方法:基于TCGA数据库中33种肿瘤的转录组、临床及突变数据,分析SERPINE2的差异表达、生存关联及免疫特征, 并通过口腔鳞状细胞癌(oral squamous cell carcinoma, OSCC)中的免疫组织化学分析、药物敏感性及侵袭实验进行验证。结果:SERPINE2在20种癌症中表达显著上调,其高表达与肿瘤患者预后呈负相关。其对肿瘤淋巴结转移的影响具有异质性;在OSCC中促进淋巴结转移。此外,SERPINE2还影响多种抗癌药物的耐药性与敏感性,药敏实验显示SERPINE2过表达降低OSCC细胞系顺铂敏感性。肿瘤微环境及空间转录组分析显示,SERPINE2表达与成纤维细胞、内皮细胞、中性粒细胞浸润呈正相关;此外,SERPINE2还与免疫检查点基因如PD-L1(CD274)、LAG3的表达明显相关。功能富集分析显示,SERPINE2相关基因主要富集于PI3K/AKT信号通路及细胞外基质-受体相互作用等转移相关通路。细胞侵袭实验证明SERPINE2过表达促进OSCC细胞侵袭性。结论:本研究表明,SERPINE2可能是泛癌预后标志物,并通过调控免疫微环境及关键信号通路促进HNSC进展,是肿瘤免疫治疗的潜在靶点。

关键词: 丝氨酸蛋白酶抑制剂E类成员2, 预后, 肿瘤微环境, 头颈部鳞状细胞癌, 泛癌分析

Abstract: Objective: To investigate the expression patterns, prognostic value, tumor microenvironment (TME) association, and correlation with lymph node metastasis of serpin family E member 2 (SERPINE2) in pan-cancer, while uncovering its potential functional pathways in head and neck squamous cell carcinoma (HNSC). Methods: Based on transcriptomic, clinical, and mutational data from 33 cancer types in the TCGA database, SERPINE2's differential expression, survival associations, and immune characteristics were analyzed. Validation was performed through immunohistochemistry (IHC), drug sensitivity assays, and invasion experiments in oral squamous cell carcinoma (OSCC). Results: SERPINE2 was significantly upregulated in 20 cancer types, and its high expression was negatively correlated with patient prognosis. Its impact on lymph node metastasis exhibited heterogeneity, and in OSCC, it promoted lymph node metastasis. Additionally, SERPINE2 influenced resistance and sensitivity to multiple anticancer drugs, with drug sensitivity assays showing that SERPINE2 overexpression reduced cisplatin sensitivity in OSCC cell lines. TME and spatial transcriptomic analyses revealed that SERPINE2 expression positively correlated with fibroblast, endothelial cell, and neutrophil infiltration. Furthermore, SERPINE2 was significantly associated with immune checkpoint genes such as PD-L1 (CD274) and LAG3. Functional enrichment analysis indicated that SERPINE2-related genes were primarily involved in metastasis-associated pathways, including the PI3K/AKT signaling pathway and extracellular matrix-receptor interactions. Cell invasion assays confirmed that SERPINE2 overexpression enhanced OSCC cell invasiveness. Conclusion: SERPINE2 may serve as a pan-cancer prognostic biomarker and promotes HNSC progression by modulating the immune microenvironment and key signaling pathways, suggesting its potential as a target for cancer immunotherapy.

Key words: serpin family E member 2, prognosis, tumor microenvironment, head and neck squamous cell carcinoma, pan-cancer analysis