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

Zhonghua Li², Haoxi Cai³, Jinyang Zheng⁴, Xun Chen⁵, Guancheng Liu⁶, Yunxia Lv⁷, Hui Ye¹, Gengming Cai^1,^8,⁹

¹Haicang Hospital Affiliated of Xiamen Medical College, Xiamen 361026, China
²Department of Otolaryngology Head and Neck Surgery, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou 362000, China
³School of Stomatology, Ningxia Medical University, Yinchuan 750004, China
⁴Department of Pathology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou 362000, China
⁵Department of Oral Surgery, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou 362000, China
⁶Department of Otolaryngology Head and Neck Surgery, The Hospital Affiliated of Guilin Medical College, Guilin 541000, China
⁷Department of Thyroid Surgery, The Second Affiliated Hospital to Nanchang University, Nanchang 330006, China
⁸The School of Clinical Medicine, Fujian Medical University, Fuzhou 361026, China
⁹The Graduate School of Fujian Medical University, Fuzhou 361026, China

Received: April 14, 2023Accepted: September 8, 2023Published: October 4, 2023

https://doi.org/10.18632/aging.205081

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.