Research Paper Volume 15, Issue 19 pp 10347—10369
Mitochondrial-related genes markers that predict survival in patients with head and neck squamous cell carcinoma affect immunomodulation through hypoxia, glycolysis, and angiogenesis pathways
- 1 Haicang Hospital Affiliated of Xiamen Medical College, Xiamen 361026, China
- 2 Department of Otolaryngology Head and Neck Surgery, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou 362000, China
- 3 School of Stomatology, Ningxia Medical University, Yinchuan 750004, China
- 4 Department of Pathology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou 362000, China
- 5 Department of Oral Surgery, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou 362000, China
- 6 Department of Otolaryngology Head and Neck Surgery, The Hospital Affiliated of Guilin Medical College, Guilin 541000, China
- 7 Department of Thyroid Surgery, The Second Affiliated Hospital to Nanchang University, Nanchang 330006, China
- 8 The School of Clinical Medicine, Fujian Medical University, Fuzhou 361026, China
- 9 The Graduate School of Fujian Medical University, Fuzhou 361026, China
Received: April 14, 2023 Accepted: September 8, 2023 Published: October 4, 2023
https://doi.org/10.18632/aging.205081How to Cite
Copyright: © 2023 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Mitochondria play a crucial role in the occurrence and development of tumors. We used mitochondria-related genes for consistent clustering to identify three stable molecular subtypes of head and neck squamous cell carcinoma (HNSCC) with different prognoses, mutations, and immune characteristics. Significant differences were observed in clinical characteristics, immune microenvironment, immune cell infiltration, and immune cell scores. TP53 was the most significantly mutated; cell cycle-related pathways and tumorigenesis-related pathways were activated in different subtypes. Risk modeling was conducted using a multifactor stepwise regression method, and nine genes were identified as mitochondria-related genes affecting prognosis (DKK1, EFNB2, ITGA5, AREG, EPHX3, CHGB, P4HA1, CCND1, and JCHAIN). Risk score calculations revealed significant differences in prognosis, immune cell scores, immune cell infiltration, and responses to conventional chemotherapy drugs. Glycolysis, angiogenesis, hypoxia, and tumor-related pathways were positively correlated with the RiskScore. Clinical samples were subjected to qPCR to validate the results. In this work, we constructed a prognostic model based on the mitochondrial correlation score, which well reflects the risk and positive factors for the prognosis of patients with HNSCC. This model can be used to guide individualized adjuvant and immunotherapy in patients with HNSCC.
Abbreviations
HNSC: Head and Neck Squamous Cancer; HPV: Human papillomavirus; TCGA: The Cancer Genome Atlas; GEO: Gene Expression Omnibus database; MSigDB: Molecular Signatures Database; GSEA: Gene Set Enrichment Analysis; CAF: tumor-associated fibroblasts; MDSCs: myeloid-derived suppressor cells; TAM: tumor-associated macrophages; CTLs: tumor-infiltrating cytotoxic T lymphocytes; TIDE: Tumor Immune Dysfunction and Exclusion; DCA: Decisioncurve; CNV: Copy Number Variation; SNV: Simple Nucleotide Variation; RNA-seq: Transcriptome expression data; ROC: receiver operating characteristic curve; OS: Overall Survival; ICB: Immune Checkpoint Blockade.