Identification and prognostic analysis of propionate metabolismrelated genes in head and neck squamous cell carcinoma

Shitong Zhou¹Yu Jiang¹Panhui Xiong¹Zhongwan Li²LIfeng Jia²Wei Yuan²Xiufu Liao²An Xiang²Jie Hu²Rui Luo²Hailan Mo²Hongyan Fang²Yucheng Yang^1*

• ¹First Affiliated Hospital of Chongqing Medical University, Chongqing, Chongqing Municipality, China
• ²Chongqing General Hospital, Chongqing, Chongqing, China

This study investigated the prognostic relevance of propionate metabolism-related genes (PMRGs) in head and neck squamous cell carcinoma (HNSCC). Transcriptome sequencing data from 502 HNSCC tumor samples and 44 normal tissue samples were sourced from the UCSC Xena database as the training set, complemented by two additional HNSCC datasets (GSE41613 and GSE6631) from the GEO database. A total of 603 PMRGs were curated from the GeneCards database. Differential expression analysis identified 10,185 differentially expressed genes (DEGs) in HNSCC, of which 6,298 were upregulated and 3,887 downregulated. Weighted gene co-expression network analysis (WGCNA) highlighted the green module, containing 993 genes, as most strongly associated with HNSCC (Cor = -0.43, p.adj = 2 × 10–22). By intersecting DEGs, key module genes, and PMRGs, 42 genes were identified. Univariate and multivariate Cox regression, along with LASSO analysis, further narrowed the list to four feature genes (PRKAA2, SLC7A5, GRIP2, CHGB), which were used to develop a prognostic risk model. The model demonstrated that patients in the low-risk group had extended survival in both the training and validation sets. Risk scores were significantly correlated with clinical characteristics, and a nomogram incorporating the risk score and pathological stage N showed high predictive accuracy. Enrichment analysis identified pathways, including the intestinal immune network for IgA production, and the high-risk group exhibited elevated mutation rates, as well as marked differences in immune cells, checkpoints, and cell cycles. Lastly, 12 potential therapeutic drugs were identified. This study underscores the potential of four PMRGs as biomarkers in HNSCC, providing novel insights into disease prognosis and therapeutic strategies.