Research Paper Volume 16, Issue 2 pp 985—1001
Prognostic significance of senescence-related tumor microenvironment genes in head and neck squamous cell carcinoma
- 1 Department of Otolaryngology-Head and Neck Surgery, Kyung Hee University School of Medicine, Kyung Hee University Hospital at Gangdong, Seoul, Republic of Korea
- 2 Department of Medicine (AgeTech-Service Convergence Major) College of Medicine, Kyung Hee University, Seoul, Republic of Korea
- 3 Department of Biostatistics, Epidemiology and Informatics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
- 4 Department of Oral and Maxillofacial Surgery, School of Dentistry, Kyung Hee University, Seoul, Republic of Korea
- 5 Department of Otolaryngology-Head and Neck Surgery, Kyung Hee University School of Medicine, Kyung Hee University Medical Center, Seoul, Republic of Korea
- 6 Institute for Biomedical Informatics, University of Pennsylvania, Philadelphia, PA 19104, USA
Received: August 24, 2023 Accepted: November 6, 2023 Published: December 21, 2023
https://doi.org/10.18632/aging.205346How to Cite
Copyright: © 2024 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
The impact of the senescence related microenvironment on cancer prognosis and therapeutic response remains poorly understood. In this study, we investigated the prognostic significance of senescence related tumor microenvironment genes (PSTGs) and their potential implications for immunotherapy response. Using the Cancer Genome Atlas- head and neck squamous cell carcinoma (HNSC) data, we identified two subtypes based on the expression of PSTGs, acquired from tumor-associated senescence genes, tumor microenvironment (TME)-related genes, and immune-related genes, using consensus clustering. Using the LASSO, we constructed a risk model consisting of senescence related TME core genes (STCGs). The two subtypes exhibited significant differences in prognosis, genetic alterations, methylation patterns, and enriched pathways, and immune infiltration. Our risk model stratified patients into high-risk and low-risk groups and validated in independent cohorts. The high-risk group showed poorer prognosis and immune inactivation, suggesting reduced responsiveness to immunotherapy. Additionally, we observed a significant enrichment of STCGs in stromal cells using single-cell RNA transcriptome data. Our findings highlight the importance of the senescence related TME in HNSC prognosis and response to immunotherapy. This study contributes to a deeper understanding of the complex interplay between senescence and the TME, with potential implications for precision medicine and personalized treatment approaches in HNSC.
Abbreviations
TME: tumor microenvironment; PSTGs: Prognostic senescence related TME genes; TCGA-HNSC: The Cancer Genome Atlas- HNSC; TAS: Tumor associated senescence; LASSO: least absolute shrinkage and selection operator; STCGs: senescence related TME core genes; HNSC: head and neck squamous cell carcinoma; HNC: Head and neck cancer; SASP: senescence-associated secretory phenotype; TPM: transcripts per kilobase million; KHUMC: Kyung Hee University Medical Center; TISCH: Tumor Immune Single Cell Hub; CDF: cumulative distribution function; MAF: mutation annotation format MAF; TMB: tumor mutation burden; HR: hazard ratios; CI: confidence intervals; IPS: immunophenoscore; TAMs: tumor-associated macrophages; CAFs: tumor-associated fibroblasts; MDSCs: myeloid-derived suppressor cells; CTLs: cytotoxic T lymphocytes; GO: gene ontology; EMT: epithelial-mesenchymal transition; PPARs: Peroxisome proliferator-activated receptors.