Lingke Chen,1,2,* Zheng Zhou,3,* Lian Guo,4 Zhongrun He,4 Wen Luo,5 Ying Fu,5 Qiyu Xiao,5 Bo Liu,6 Pengxin Huang1 

1Department of Head and Neck Surgery, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Hunan Cancer Hospital, Changsha, People’s Republic of China; 2Department of Stomatology, Changsha Central Hospital, Changsha, People’s Republic of China; 3Department of Otolaryngology Head and Neck Surgery, The Affiliated Children’s Hospital of Xiangya School of Medicine, Central South University, Hunan Children’s Hospital, Changsha, People’s Republic of China; 4Department of Pharmacy, Zunyi Medical University, Zunyi, People’s Republic of China; 5Department of Nuclear Medicine, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Hunan Cancer Hospital, Changsha, People’s Republic of China; 6Department of Emergency, Xi’an No.3 hospital, The Affiliated Hospital of Northwest University, Xi’an, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Bo Liu, Email hanpengbobo@sina.com Pengxin Huang, Email huangpengxin@hnca.org.cn

Background: Oral squamous cell carcinoma (OSCC) is a common head and neck cancer with high morbidity and mortality. Mitophagy is a special type of cellular autophagy that plays an important role in tumors, but its role in OSCC is still unclear.
Methods: Mitophagy-related genes (MRGs) were obtained from the GeneCards database. Differential expression analysis was used to identify differentially expressed genes (DEGs) in tumor samples and normal samples. Univariate Cox regression was then performed on the DEGs to determine prognostic MRGs, which were used to compare CNV mutation frequencies and construct consensus cluster analysis. Risk models were constructed to evaluate the prognosis and immune status of OSCC patients. Univariate and multivariate Cox regression analyses were performed to determine MRGs that independently predicted OSCC prognosis. The expression levels of genes and their effects on OSCC proliferation, migration, and invasion were further validated by in vitro and in vivo studies.
Results: We identified 298 DEGs associated with OSCC survival, and 8 genes were used to create a risk model that can accurately predict the prognosis of OSCC patients, which can accurately assess the immune status of patients with different risks. OSCC patients were clustered into 2 subtypes, and there were significant differences between the two subtypes. Drug sensitivity analysis was used to select 72 sensitive drugs for the low-risk group and 9 sensitive drugs for the high-risk group. Choline dehydrogenase (CHDH) was identified as a reliable and independent predictor of OSCC. CHDH overexpression significantly inhibited OSCC cell proliferation, migration, colony formation, and tumor growth.
Conclusion: This study’s prediction model, created using MRGs, may accurately predict the prognosis and immune response of patients with OSCC. CHDH is essential to the development and progression of OSCC and can be a potential target for treating OSCC.

Keywords: mitophagy, oral squamous cell carcinoma, proliferation, immune response, prognosis, Choline dehydrogenase (CHDH)