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

doi:10.13701/j.cnki.kqyxyj.2026.06.004

Abstract

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

MA Jiyuan, NONG Sheng, PAN Junchen, SUN Yanan, ZHANG Jiali. Pan-cancer Analysis of SERPINE2 and Its Association with Tumor Microenvironment in Head and Neck Squamous Cell Carcinoma[J]. Journal of Oral Science Research, 2026, 42(6): 478-486.

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