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构建用于预测乳腺癌预后和免疫反应的脂肪酸代谢相关基因特征。

Construction of a fatty acid metabolism-related gene signature for predicting prognosis and immune response in breast cancer.

作者信息

Qian Li, Liu Yi-Fei, Lu Shu-Min, Yang Juan-Juan, Miao Hua-Jie, He Xin, Huang Hua, Zhang Jian-Guo

机构信息

Department of Pathology, Affiliated Hospital of Nantong University, Nantong, China.

Department of Oncology, Shanghai Jiaotong University School of Medicine Xinhua Hospital, Shanghai, China.

出版信息

Front Genet. 2023 Mar 1;14:1002157. doi: 10.3389/fgene.2023.1002157. eCollection 2023.

Abstract

Breast cancer has the highest incidence among malignant tumors in women, and its prevalence ranks first in global cancer morbidity. This study aimed to explore the feasibility of a prognostic model for patients with breast cancer based on the differential expression of genes related to fatty acid metabolism. The mRNA expression matrix of breast cancer and paracancer tissues was downloaded from The Cancer Genome Atlas database. The differentially expressed genes related to fatty acid metabolism were screened in R language. The TRRUST database was used to predict transcriptional regulators related to hub genes and construct an mRNA-transcription factor interaction network. A consensus clustering approach was used to identify different fatty acid regulatory patterns. In combination with patient survival data, Lasso and multivariate Cox proportional risk regression models were used to establish polygenic prognostic models based on fatty acid metabolism. The median risk score was used to categorize patients into high- and low-risk groups. Kaplan-Meier survival curves were used to analyze the survival differences between both groups. The Cox regression analysis included risk score and clinicopathological factors to determine whether risk score was an independent risk factor. Models based on genes associated with fatty acid metabolism were evaluated using receiver operating characteristic curves. A comparison was made between risk score levels and the fatty acid metabolism-associated genes in different subtypes of breast cancer. The differential gene sets of the Kyoto Encyclopedia of Genes and Genomes for screening high- and low-risk populations were compared using a gene set enrichment analysis. Furthermore, we utilized CIBERSORT to examine the abundance of immune cells in breast cancer in different clustering models. High expression levels of ALDH1A1 and UBE2L6 prevented breast cancer, whereas high RDH16 expression levels increased its risk. Our comprehensive assessment of the association between prognostic risk scoring models and tumor microenvironment characteristics showed significant differences in the abundance of various immune cells between high- and low-risk breast cancer patients. By assessing fatty acid metabolism patterns, we gained a better understanding of the infiltration characteristics of the tumor microenvironment. Our findings are valuable for prognosis prediction and treatment of patients with breast cancer based on their clinicopathological characteristics.

摘要

乳腺癌在女性恶性肿瘤中的发病率最高,其患病率在全球癌症发病率中排名第一。本研究旨在探讨基于脂肪酸代谢相关基因差异表达的乳腺癌患者预后模型的可行性。从癌症基因组图谱数据库下载乳腺癌和癌旁组织的mRNA表达矩阵。用R语言筛选与脂肪酸代谢相关的差异表达基因。利用TRRUST数据库预测与枢纽基因相关的转录调节因子,并构建mRNA-转录因子相互作用网络。采用一致性聚类方法识别不同的脂肪酸调节模式。结合患者生存数据,使用Lasso和多变量Cox比例风险回归模型建立基于脂肪酸代谢的多基因预后模型。用中位风险评分将患者分为高风险组和低风险组。采用Kaplan-Meier生存曲线分析两组之间的生存差异。Cox回归分析纳入风险评分和临床病理因素,以确定风险评分是否为独立危险因素。使用受试者工作特征曲线评估基于脂肪酸代谢相关基因的模型。比较了不同亚型乳腺癌的风险评分水平与脂肪酸代谢相关基因。使用基因集富集分析比较京都基因与基因组百科全书中用于筛选高风险和低风险人群的差异基因集。此外,我们利用CIBERSORT检测不同聚类模型中乳腺癌免疫细胞的丰度。ALDH1A1和UBE2L6的高表达可预防乳腺癌,而RDH16的高表达则增加其风险。我们对预后风险评分模型与肿瘤微环境特征之间关联的综合评估显示,高风险和低风险乳腺癌患者的各种免疫细胞丰度存在显著差异。通过评估脂肪酸代谢模式,我们对肿瘤微环境的浸润特征有了更好的理解。我们的研究结果对于基于临床病理特征的乳腺癌患者预后预测和治疗具有重要价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31c6/10014556/aecf68aab1cb/fgene-14-1002157-g001.jpg

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