TGF-β Signaling Pathway-Based Model to Predict the Subtype and Prognosis of Head and Neck Squamous Cell Carcinoma
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Updated: Sep 22, 2025

A Model for Perineural Invasion in Head and Neck Squamous Cell Carcinoma
Published on: January 5, 2017
Lian Zheng1, Zhenjie Guan2, Miaomiao Xue3
1Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Abstract:
Background: Although immunotherapy with immune checkpoint therapy has been used to treat head and neck squamous cell carcinoma (HNSCC), response rates and treatment sensitivity remain limited. Recent studies have indicated that transforming growth factor-β (TGF-β) may be an important target for novel cancer immunotherapies. Materials and methods: We collected genomic profile data from The Cancer Genome Atlas and Gene Expression Omnibus. The least absolute shrinkage and selection operator method and Cox regression were used to establish a prognostic model. Gene set enrichment analysis was applied to explore biological functions. Tracking of indels by decomposition and subclass mapping algorithms were adopted to evaluate immunotherapy efficiency. Result: We established a seven TGF-β pathway-associated gene signature with good prediction efficiency. The high-risk score subgroup mainly showed enrichment in tumor-associated signaling such as hypoxia and epithelial-mesenchymal transition (EMT) pathways; This subgroup was also associated with tumor progression. The low-risk score subgroup was more sensitive to immunotherapy and the high-risk score subgroup to cisplatin, erlotinib, paclitaxel, and crizotinib. Conclusion: The TGF-β pathway signature gene model provides a novel perspective for evaluating effectiveness pre-immunotherapy and may guide further studies of precision immuno-oncology.
Insights
A new seven-gene signature targeting the transforming growth factor-β (TGF-β) pathway improves head and neck squamous cell carcinoma (HNSCC) treatment prediction. This signature helps identify patients likely to respond to immunotherapy or specific chemotherapies.
Area of Science:
- Oncology
- Immunotherapy
- Genomics
Background:
- Immune checkpoint therapy for head and neck squamous cell carcinoma (HNSCC) has limited response rates.
- Transforming growth factor-β (TGF-β) is a potential target for enhancing cancer immunotherapies.
Purpose of the Study:
- To develop a prognostic model for HNSCC based on TGF-β pathway-associated genes.
- To evaluate the predictive value of this model for immunotherapy and chemotherapy response.
Main Methods:
- Utilized genomic data from The Cancer Genome Atlas and Gene Expression Omnibus.
- Employed least absolute shrinkage and selection operator (LASSO) and Cox regression for model building.
- Applied gene set enrichment analysis and specific algorithms to assess immunotherapy efficiency.
Main Results:
- A seven-gene signature associated with the TGF-β pathway was established with high predictive accuracy.
- High-risk patients showed enrichment in hypoxia and epithelial-mesenchymal transition (EMT) pathways, correlating with tumor progression.
- Low-risk patients were more sensitive to immunotherapy, while high-risk patients responded better to cisplatin, erlotinib, paclitaxel, and crizotinib.
Conclusions:
- The TGF-β pathway signature offers a new approach for predicting pre-immunotherapy effectiveness in HNSCC.
- This model may guide precision immuno-oncology strategies and future research.
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