Department of Gastroenterology, Strategic Support Force Medical Center, Beijing 100101, China.
Department of Spinal Surgery, Strategic Support Force Medical Center, Beijing 100101, China.
Aging (Albany NY). 2024 May 13;16(10):8552-8571. doi: 10.18632/aging.205823.
Fatty acid metabolism (FAM) contributes to tumorigenesis and tumor development, but the role of FAM in the progression of stomach adenocarcinoma (STAD) has not been comprehensively clarified.
The expression data and clinical follow-up information were obtained from The Cancer Genome Atlas (TCGA). FAM pathway was analyzed by gene set enrichment analysis (GSEA) and single-sample GSEA (ssGSEA) methods. Univariate Cox regression analysis was conducted to select prognosis genes. Molecular subtypes were classified by consensus clustering analysis. Furthermore, least absolute shrinkage and selection operator (Lasso) analysis was employed to develop a risk model. ESTIMATE and tumour immune dysfunction and exclusion (TIDE) algorithm were used to assess immunity. pRRophetic package was conducted to predict drug sensitivity.
Based on 14 FAM related prognosis genes (FAMRG), 2 clusters were determined. Patients in C2 showed a worse overall survival (OS). Furthermore, a 7-FAMRG risk model was established as an independent predictor for STAD, with a higher riskscore indicating an unfavorable OS. High riskscore patients had higher TIDE score and these patients were more sensitive to anticancer drugs such as Bortezomib, Dasatinib and Pazopanib. A nomogram based on riskscore was an effective prediction tool applicable to clinical settings. The results from pan-cancer analysis supported a prominent application value of riskscore model in other cancer types.
The FAMRGs model established in this study could help predict STAD prognosis and offer new directions for future studies on dysfunctional FAM-induced damage and anti-tumor drugs in STAD disease.
脂肪酸代谢(FAM)有助于肿瘤发生和肿瘤发展,但 FAM 在胃腺癌(STAD)进展中的作用尚未得到全面阐明。
从癌症基因组图谱(TCGA)中获取表达数据和临床随访信息。采用基因集富集分析(GSEA)和单样本 GSEA(ssGSEA)方法分析 FAM 通路。通过单因素 Cox 回归分析选择预后基因。采用共识聚类分析对分子亚型进行分类。此外,采用最小绝对收缩和选择算子(Lasso)分析建立风险模型。ESTIMATE 和肿瘤免疫功能障碍和排斥(TIDE)算法用于评估免疫。采用 pRRophetic 包预测药物敏感性。
基于 14 个与 FAM 相关的预后基因(FAMRG),确定了 2 个簇。C2 组患者的总生存期(OS)更差。此外,建立了一个由 7 个 FAMRG 组成的风险模型,作为 STAD 的独立预测因子,风险评分越高,OS 越差。高风险评分患者的 TIDE 评分更高,这些患者对硼替佐米、达沙替尼和帕唑帕尼等抗癌药物更敏感。基于风险评分的列线图是一种有效的预测工具,适用于临床环境。泛癌分析的结果支持风险评分模型在其他癌症类型中的突出应用价值。
本研究建立的 FAMRGs 模型有助于预测 STAD 的预后,并为未来研究 FAM 诱导的功能障碍损伤和 STAD 疾病中的抗肿瘤药物提供新的方向。