AUTHOR=Zhou Shitong , Jiang Yu , Xiong Panhui , Li Zhongwan , Jia Lifeng , Yuan Wei , Liao Xiufu , An Xiang , Hu Jie , Luo Rui , Mo Hailan , Fang Hongyan , Yang Yucheng 

TITLE=Identification and prognostic analysis of propionate metabolism-related genes in head and neck squamous cell carcinoma

JOURNAL=Frontiers in Oncology

VOLUME=Volume 15 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1518587

DOI=10.3389/fonc.2025.1518587

ISSN=2234-943X

ABSTRACT=IntroductionHead and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous malignancy with poor overall prognosis. Recent studies have suggested that propionate metabolism-related genes (PMRGs) may play key roles in tumor progression and immune regulation, yet their functions in HNSCC remain unclear.MethodsTranscriptomic data from 502 HNSCC tumor samples and 44 normal tissue samples were obtained from the UCSC Xena database as the training set. Two independent datasets (GSE41613 and GSE6631) from the GEO database were used for validation. Differentially expressed genes (DEGs), key module genes identified via weighted gene co-expression network analysis (WGCNA), and PMRGs were intersected to identify candidate genes. A prognostic model was constructed using Cox regression and LASSO analysis. Immune infiltration, somatic mutations, and drug sensitivity were compared between high- and low-risk groups. Gene expression was further validated by RT-qPCR using clinical samples.ResultsA total of 42 intersecting genes were identified, and four feature genes (PRKAA2, SLC7A5, GRIP2, CHGB) were selected to build the prognostic model. The model effectively stratified patients into high- and low-risk groups with significant survival differences in both the training and validation cohorts. The high-risk group exhibited marked differences in immune cell infiltration, immune checkpoint expression, and cancer immune cycle activity. Mutation burden and drug sensitivity also varied significantly between risk groups. A nomogram combining risk score and pathological N stage showed strong predictive performance.DiscussionThis study highlights the potential role of PMRGs in immune regulation and tumor progression in HNSCC. The proposed four-gene signature provides a novel tool for prognosis prediction and offers new insights for risk stratification and individualized therapy. Further multicenter validation and mechanistic studies are warranted.