Department of ORL-HNS, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai 201804, China.
Department of Biochemistry and Molecular Biology, School of Medicine, Tongji University, Shanghai 201804, China.
Int J Mol Sci. 2023 Jul 21;24(14):11753. doi: 10.3390/ijms241411753.
Amino acid metabolism has been implicated in tumorigenesis and tumor progression. Alterations in intracellular and extracellular metabolites associated with metabolic reprogramming in cancer have profound effects on gene expression, cell differentiation, and tumor immune microenvironment. However, the prognostic significance of amino acid metabolism in head and neck cancer remains to be further investigated. In this study, we identified 98 differentially expressed genes related to amino acid metabolism in head and neck cancer in The Cancer Genome Atlas. Using batch univariate Cox regression and Lasso regression, we extracted nine amino acid metabolism-related genes. Based on that, we developed the amino acid metabolism index. The prognostic value of this index was validated in two Gene Expression Omnibus cohorts. The results show that this model can help predict tumor recurrence and prognosis. The infiltration of immune cells in the tumor microenvironment was analyzed, and it was discovered that the high index is associated with an immunosuppressive microenvironment. In addition, this study demonstrated the impact of the amino acid metabolism index on clinical indicators, survival of patients with head and neck cancer, and the prediction of treatment response to immune checkpoint inhibitors. We conducted several cell experiments and demonstrated that epigenetic drugs could affect the index and enhance tumor immunity. In conclusion, our study demonstrates that the index not only has important prognostic value in head and neck cancer patients but also facilitates patient stratification for immunotherapy.
氨基酸代谢与肿瘤发生和肿瘤进展有关。与癌症代谢重编程相关的细胞内和细胞外代谢物的改变，对基因表达、细胞分化和肿瘤免疫微环境有深远的影响。然而，氨基酸代谢在头颈部癌症中的预后意义仍有待进一步研究。在这项研究中，我们在癌症基因组图谱中鉴定了 98 个与头颈部癌症中氨基酸代谢相关的差异表达基因。使用批量单变量 Cox 回归和 Lasso 回归，我们提取了 9 个与氨基酸代谢相关的基因。基于此，我们开发了氨基酸代谢指数。该指数的预后价值在两个基因表达综合数据集队列中得到了验证。结果表明，该模型可以帮助预测肿瘤复发和预后。分析了肿瘤微环境中免疫细胞的浸润情况，发现高指数与免疫抑制微环境有关。此外，这项研究还证明了氨基酸代谢指数对临床指标、头颈部癌症患者的生存以及免疫检查点抑制剂治疗反应的预测的影响。我们进行了一些细胞实验，证明了表观遗传药物可以影响该指数并增强肿瘤免疫。总之，我们的研究表明，该指数不仅对头颈部癌症患者具有重要的预后价值，而且有助于对免疫治疗进行患者分层。
