Thyroid Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Sci Rep. 2022 Nov 5;12(1):18809. doi: 10.1038/s41598-022-23500-6.
Laryngeal cancer is the second most prevalent head and neck tumor and it is one of the most common malignancies of the upper respiratory tract. Fatty acid metabolism affects cancer cell biology in several ways, and alterations in fatty acid metabolism are characteristic of both tumorigenesis and metastasis. Despite advances in laryngeal cancer diagnosis and treatment over the years, there has been no significant improvement in survival or mortality. Studying the role of fatty acid metabolism-related genes in laryngeal cancer will facilitate our search for valuable biomarkers to guide prognostic management and treatment selection. We constructed a prognostic risk score model for fatty acid metabolism-related genes by downloading and analyzing laryngeal cancers from the TCGA and GEO databases. We predicted survival outcomes of laryngeal cancer patients using a prognostic risk score model of fatty acid metabolism-related genes and analyzed the resistance of laryngeal cancer in different individuals to multiple drugs. In addition, the relationship between the prognostic risk score model and cellular infiltration characteristics of the tumor microenvironment were investigated. Through the prognostic risk scoring model, the genes with risk-prompting effect and related to prognosis were screened out for further research. Through the study of gene expression levels in the TCGA database, we screened out 120 differentially expressed fatty acid metabolism genes. LASSO-Cox and Cox regression analyses identified nine genes associated with prognosis to construct a prognostic risk score model for genes related to fatty acid metabolism. Both TCGA and GEO confirmed that samples in the high-risk score group had a worse prognosis than those in the low-risk score group. We found significant differences between the high-risk and low-risk groups for 22 drugs (P < 0.05). In addition, we found differences in immune cell infiltration between the different risk score groups. Finally, through the risk assessment model, combined with multiple databases, THBS1, a high-risk and prognosis-related gene, was screened. We also found that THBS1 could promote the migration, invasion and proliferation of laryngeal cancer cells by constructing THBS1 knockout cell lines. In our study, we identified key fatty acid-related genes differentially expressed in laryngeal carcinoma that can be used to adequately predict prognosis using a comprehensive bioinformatic experimental approach. It was also found that THBS1, a high-risk and prognosis-related gene, may regulate the occurrence and development of laryngeal cancer through fatty acid metabolism, which has further helped us to explore the role of fatty acid metabolism genes in laryngeal cancer.
喉癌是第二大常见的头颈部肿瘤,也是上呼吸道最常见的恶性肿瘤之一。脂肪酸代谢通过多种方式影响癌细胞生物学,并且脂肪酸代谢的改变是肿瘤发生和转移的特征。尽管近年来在喉癌的诊断和治疗方面取得了进展,但在生存率或死亡率方面并没有显著改善。研究脂肪酸代谢相关基因在喉癌中的作用将有助于我们寻找有价值的生物标志物来指导预后管理和治疗选择。我们通过下载和分析 TCGA 和 GEO 数据库中的喉癌数据,构建了一个脂肪酸代谢相关基因的预后风险评分模型。我们使用脂肪酸代谢相关基因的预后风险评分模型预测喉癌患者的生存结果,并分析不同个体对多种药物的喉癌耐药性。此外,还研究了预后风险评分模型与肿瘤微环境细胞浸润特征的关系。通过预后风险评分模型,筛选出具有风险提示作用且与预后相关的基因进行进一步研究。通过 TCGA 数据库中基因表达水平的研究,筛选出 120 个差异表达的脂肪酸代谢基因。LASSO-Cox 和 Cox 回归分析确定了 9 个与预后相关的基因,构建了脂肪酸代谢相关基因的预后风险评分模型。TCGA 和 GEO 均证实高风险评分组的样本预后比低风险评分组差。我们发现高风险组和低风险组之间 22 种药物的差异有统计学意义(P<0.05)。此外,我们还发现不同风险评分组之间的免疫细胞浸润存在差异。最后,通过风险评估模型,结合多个数据库,筛选出与 THBS1 高风险和预后相关的基因。我们还发现通过构建 THBS1 敲除细胞系,THBS1 可以促进喉癌细胞的迁移、侵袭和增殖。在我们的研究中,我们通过综合生物信息学实验方法,确定了在喉癌中差异表达的关键脂肪酸相关基因,这些基因可以充分预测预后。还发现与 THBS1 高风险和预后相关的基因可能通过脂肪酸代谢调节喉癌的发生和发展,这进一步帮助我们探讨了脂肪酸代谢基因在喉癌中的作用。