Abstract
Research on prognostic factors for oral squamous cell carcinoma (OSCC) has revealed new therapeutic targets, with angiogenesis playing a key role in tumor development, invasion, and prognosis. However, reports on OSCC prognostic prediction construction based on angiogenesis factors are limited. Through bioinformatics analysis, we aimed to identify angiogenesis factors whose expression changes may be linked to OSCC prognosis. RNA sequencing, clinical data, and angiogenesis factor data were obtained from The Cancer Genome Atlas and Molecular Signatures Database. The characterized gene was selected and analyzed for correlations with clinicopathological features, prognosis, and cancer-associated fibroblasts infiltration using various databases. Further analyses included gene mutation, functional enrichment, and validation using clinical OSCC samples and tumor-bearing nude mice. Gene expression was assessed by western blotting, immunohistochemistry, immunofluorescence, and quantitative reverse transcription polymerase chain reaction. Epidermal growth factor (EGF) emerged as a key gene, showing significant upregulation in OSCC tissues compared to normal oral mucosa. Univariate and multivariate Cox regression analyses confirmed that high EGF expression correlates with poor overall survival and serves as an independent prognostic factor. EGF was also linked to cancer-associated fibroblast infiltration and can influence angiogenesis pathways. Our findings indicate that EGF may serve as a prognostic biomarker and potential therapeutic target for OSCC.
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Abbreviations
- OSCC:
-
Oral squamous cell carcinoma
- TCGA:
-
The Cancer Genome Atlas
- TNM:
-
Tumor-Node-Metastasis
- EGF:
-
Epidermal growth factor
- DEGs:
-
Differentially expressed genes
- OS:
-
Overall survival
- CAFs:
-
Cancer-associated fibroblasts
- XCELL:
-
X for Cell type identification based on Expression Level Landscape
- TIDE:
-
Tumor Immune Dysfunction and Exclusion
- EPIC:
-
Estimate the Proportion of Immune and Cancer cells
- MCPCOUNT:
-
Microenvironment Cell Populations Counter
- STRING:
-
The Search Tool for the Retrieval of Interacting Genes/Proteins
- GO:
-
Gene Ontology
- KEGG:
-
Kyoto Encyclopedia of Genes and Genomes
- GESA:
-
Gene Set Enrichment Analysis
- GEPIA2:
-
Gene Expression Profiling Interactive Analysis 2
- ULCAN:
-
The University of Alabama at Birmingham Database
- ROC:
-
Receiver operating characteristic
- AUC:
-
The area under the curve
- RT-qPCR:
-
Quantitative reverse transcription polymerase chain reaction
- EGFR:
-
Epidermal growth factor receptor
- HNSC:
-
Head and neck squamous cell carcinoma
- RNA-seq:
-
RNA sequencing
- FDR:
-
False discovery rate
- P. adj:
-
Adjusted P value
- NES:
-
Normalized enrichment score
- GAPDH:
-
Glyceraldehyde-3-phosphate dehydrogenase
- NOM:
-
Normal oral mucosa
- SCC:
-
Squamous cell carcinoma
- CI:
-
Confidence interval
- 95% CI:
-
95% confidence interval
- HR:
-
hazard ratio
- TMEM:
-
Transmembrane
- EMT:
-
Epithelial-mesenchymal transition
Acknowledgements
The authors are grateful to all patients participating in our research project.
Funding
This study was supported by the National Natural Science Foundation of China (grant number: 82401112), Health Commission of Sichuan Province Medical Science and Technology Program (grant number: 25LCYJ02), Special Fund Project of The Affiliated Stomatological Hospital of Southwest Medical University-Key Support Plan for Basic Research (grant number: 2025KQZX03), the tutor ability enhancement program of The Affiliated Stomatological Hospital of Southwest Medical University (grant number: 2025DS12) and the “RYTIME Foundation” scientific research and cultivation program of The Affiliated Stomatological Hospital of Southwest Medical University (grant number: 2022RT07). These funding sources were used to conduct the research and prepare this article.
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The authors declare no competing interests.
Ethical approval Clinical specimens and consent to participate
The clinical samples were collected in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki). Clinical specimen collection was performed in compliance with national laws and institutional guidelines, and was approved by the Regional Ethical Committee (The Affiliated Stomatological Hospital of Southwest Medical University Ethics Committee, Luzhou, China, grant number:20220809001). Prior to participation, patients or their guardians provided written informed consent. The privacy rights of patients and their guardians were observed.
Animal experiments
Animal studies were approved by the Animal Welfare and Research Ethics Committee of Southwest Medical University (grant number: 20240122-003), and animal experiments were conducted in accordance with institutional and national regulations. All experiments complied with the China Animal Welfare Legislation, ARRIVE guidelines, the U.K. Animals (Scientific Procedures) Act of 1986 and associated guidelines, EU Directive 2010/63/EU for animal experiments and the National Research Council’s Guide for the Care and Use of Laboratory Animals.
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He, L., Shi, L., Wei, J. et al. Integrated bioinformatics approaches and expression assays identified a potential prognostic biomarker in oral squamous cell carcinoma. Sci Rep (2026). https://doi.org/10.1038/s41598-026-51806-2
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DOI: https://doi.org/10.1038/s41598-026-51806-2
