Dai Yifei, Chen Xiantao, Sui Xin, Li Yushen, Xin Jiajun, Zou Jiatong, Wang Rui, Liu Zhihui
Hospital of Stomatology, Jilin University, Changchun, People' s Republic of China.
Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Changchun, People' s Republic of China.
Medicine (Baltimore). 2025 Jun 13;104(24):e42665. doi: 10.1097/MD.0000000000042665.
Hypoxia and lactate metabolism are both distinctive characteristics of cancerous cells. Head and neck squamous cell carcinoma (HNSCC) is one of the most prevalent forms of cancer. The objective of this study was to construct a prognostic model of genes related to hypoxia and lactate metabolism in order to facilitate the study of the prognosis, tumor immune microenvironment and therapeutic response of patients with HNSCC. The RNA-seq and clinical data for HNSCC were obtained from The Cancer Genome Atlas database and gene expression omnibus. The hypoxia- and lactate metabolism-related genes were obtained from the Molecular Signatures Database. The identification of differentially expressed genes was conducted using the "limma" R package. Subsequently, protein-protein interaction networks of the differentially expressed genes were constructed using the STRING database and Cytoscape software. A hypoxia-lactate metabolism-related prognostic model was constructed through the application of univariate Cox regression, random survival forest, and stepwise multivariate Cox regression analyses. Subsequently, further analyses were conducted, including principal component analysis, gene enrichment analysis, CIBERSORT (Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts), ImmuCellAI, ESTIMATE, tumor immune dysfunction and exclusion, IPS, oncoPredict, and CellMiner. These were performed to analyze the differences in immune landscapes and treatment responses. The results of our study demonstrate that hypoxia- and lactate metabolism-related features are promising biomarkers for predicting outcomes in patients with HNSCC.
缺氧和乳酸代谢都是癌细胞的显著特征。头颈部鳞状细胞癌（HNSCC）是最常见的癌症形式之一。本研究的目的是构建一个与缺氧和乳酸代谢相关的基因预后模型，以促进对HNSCC患者的预后、肿瘤免疫微环境和治疗反应的研究。HNSCC的RNA测序和临床数据来自癌症基因组图谱数据库和基因表达综合数据库。与缺氧和乳酸代谢相关的基因从分子特征数据库中获取。使用“limma”R包进行差异表达基因的鉴定。随后，使用STRING数据库和Cytoscape软件构建差异表达基因的蛋白质-蛋白质相互作用网络。通过应用单变量Cox回归、随机生存森林和逐步多变量Cox回归分析构建缺氧-乳酸代谢相关的预后模型。随后，进行了进一步的分析，包括主成分分析、基因富集分析、CIBERSORT（通过估计RNA转录本的相对子集进行细胞类型鉴定）、ImmuCellAI、ESTIMATE、肿瘤免疫功能障碍和排除、IPS、肿瘤预测和CellMiner。进行这些分析是为了分析免疫景观和治疗反应的差异。我们的研究结果表明，与缺氧和乳酸代谢相关的特征是预测HNSCC患者预后的有前景的生物标志物。
