目的:探讨脂肪酸氧化(FAO)相关基因在预测头颈部鳞状细胞癌(HNSCC)进展及预后中的作用。
方法:采用Cox回归分析建立FAO相关基因预后模型,在此期间,在癌症基因组图谱(TCGA)内部测试和基因表达综合(GEO)外部验证队列中评估了基因模型的准确性和敏感性.最终,使用STRING和Cytoscape在13个模型基因中鉴定出hub基因,通过免疫组织化学进行了初步验证。
结果:模型,其中包含13个基因(ABCD2,ACAA1,ACACB,AKT1,CNR1,CPT1C,Crot,ECHDC2,ETFA,哈德赫,IRS2、LONP2和SLC25A17),已建立。根据中位数风险评分,在随后的测试和验证中,将这两个队列分为低风险和高风险组,前者的生存率明显高于后者。列线图是根据预后因素建立的,包括阶段和风险评分,并对HNSCC患者进行个体化预测。最终,免疫组化染色显示ACAA1和HADHB在HNSCC中显著低表达,与低HADHB和高ACAA1相关的良好预后。
结论:基因预后模型在预测预后方面显示了有希望的能力,ACAA1和HADHB可能作为HNSCC患者的潜在治疗生物标志物。
OBJECTIVE: To investigate the importance of fatty acid oxidation (FAO)-related genes in predicting the progression and prognosis of head and neck squamous cell carcinoma (HNSCC).
METHODS: The FAO-related gene prognostic model was established employing Cox regression analyses, during which accuracy and sensitivity of the gene model were evaluated in The Cancer Genome Atlas (TCGA) internal testing and Gene Expression Omnibus (GEO) external validation cohorts. Ultimately, hub genes were identified among 13 model genes using STRING and Cytoscape, with preliminary validation carried out through immunohistochemistry.
RESULTS: The model, which comprised 13 genes (ABCD2, ACAA1, ACACB, AKT1, CNR1, CPT1C, CROT, ECHDC2, ETFA, HADHB, IRS2, LONP2, and SLC25A17), was established. On the basis of the median risk score, the two cohorts were grouped into low-and high-risk groups in the subsequent test and validation, and the former exhibited significantly higher survival rates than the latter. Nomograms were established based on prognostic factors, including stage and risk score, and individualized for the prediction of HNSCC patients. Ultimately, immunohistochemical staining showed that ACAA1 and HADHB were significantly under-expressed in HNSCC, with a favorable prognosis associated with low HADHB and high ACAA1.
CONCLUSIONS: The gene prognostic model has illustrated promising capability in predicting the prognosis, and ACAA1 and HADHB might serve as potential therapeutic biomarkers for HNSCC patients.