脂肪酸代谢是癌症研究不可或缺的一部分，因为其在癌症诱导和进展中的作用。然而，在直肠腺癌中，其特征和预后价值尚未得到系统评估。我们从肿瘤基因组图谱和基因表达引物数据库中收集了脂肪酸代谢基因表达谱和临床信息。在排除缺乏临床信息和存在基因突变的个体后，我们对剩下的病人进行了一致聚类，并选择了稳定的聚类结果来分组病人。比较亚组之间的差异表达基因和基因集富集分析，同时进行代谢特征识别和肿瘤微环境解码。此外，我们探究了不同亚组病人的生存状况，并通过最小绝对收缩和选择算子回归法鉴定影响生存的签名基因。最后，我们选取了签名基因通过多因素Cox回归构建危险预测模型，并通过一元Cox回归和受试者工作特征曲线评估模型效能。通过一致聚类，患者被划分为2个稳定的亚群，基因集富集分析和代谢特征识别有效地定义了2个完全不同的脂肪酸代谢亚型：脂肪酸分解亚型和脂肪酸合成亚型。其中，脂肪酸分解亚型的患者预后较差，在肿瘤微环境中有显著较低的髓样树突状细胞浸润。水通道蛋白7（风险比，HR = 2.064（1.4408-4.5038）; P < .01）、X不活化特异性转录本（HR =（0.3758-0.7564），P = .045）和白细胞介素4诱导1（HR = 1.34（1.13-1.59）; P = .034）通过多因素Cox回归被选定，构建了风险预测模型。模型的独立风险比为2.72，曲线下面积高于年龄、性别和肿瘤分期，展现出更好的预测效能。我们的研究揭示了直肠腺癌中脂肪酸代谢的异质性，定义了2个完全不同的脂肪酸代谢亚型，并建立了一种新的与脂肪酸代谢相关的风险预后模型。本研究为个体风险评估和监测提供了支持，为个体化治疗提供了数据。版权所有© 2023作者。 Wolters Kluwer Health， Inc. 发布。

Fatty acid metabolism is an essential part of cancer research due to its role in cancer initiation and progression. However, its characteristics and prognostic value in rectum adenocarcinoma have not been systematically evaluated. We collected fatty acid metabolism gene expression profiles and clinical information from the cancer genome atlas and gene expression omnibus databases. After excluding individuals lacking clinical information and the presence of genetic mutations, we performed consistent clustering of the remaining patients and selected stable clustering results to group patients. Differentially expressed genes and gene set enrichment analysis were compared between subgroups, while metabolic signature identification and decoding the tumor microenvironment were performed. In addition, we explored the survival status of patients among different subgroups and identified signature genes affecting survival by least absolute shrinkage and selection operator regression. Finally, we selected signature genes to construct a risk prognostic model by multivariate Cox regression and evaluated model efficacy by univariate Cox regression and the receiver operating characteristic curve. By consensus clustering, patients were distinguished into 2 stable subpopulations, gene set enrichment analysis and metabolic signature identification effectively defined 2 completely different subtypes of fatty acid metabolism: fatty acid catabolic subtype and fatty acid anabolic subtype. Among them, patients with the fatty acid catabolic subtype had a poorer prognosis, with a significantly lower proportion of myeloid dendritic cells infiltration within the tumor microenvironment. Aquaporin 7 (hazard ratio, HR = 2.064 (1.4408-4.5038); P < .01), X inactive specific transcript (HR = (0.3758-0.7564), P = .045) and interleukin 4 induced 1 (HR = 1.34 (1.13-1.59); P = .034), were selected by multivariate Cox regression, which constructed a risk prognostic model. The independent hazard ratio of the model was 2.72 and the area under curve was higher than age, gender and tumor stage, showing better predictive efficacy. Our study revealed the heterogeneity of fatty acid metabolism in rectum adenocarcinoma, defined 2 completely distinct subtypes of fatty acid metabolism, and finally established a novel fatty acid metabolism-related risk prognostic model. The study contributes to the early risk assessment and monitoring of individual prognosis and provides data to support individualized patient treatment.Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.