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通过整合生物信息学研究花生四烯酸代谢在乳腺癌中的预后价值

英文原题:The prognostic value of arachidonic acid metabolism in breast cancer by integrated bioinformatics.

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The prognostic value of arachidonic acid metabolism in breast cancer by integrated bioinformatics.

PubMed 2022/10/15(内容时间) Lipids Health Dis Q1 · IF 6.9(JCR 2025)

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研究概要

研究表明,高水平的 AA 代谢可能是乳腺癌良好预后的生物标志物,为环氧化酶抑制剂在癌症治疗中效果不佳提供了一种可能的解释。此外,该研究构建了一种新的 AA 代谢预后特征,为乳腺癌提供了一种新策略。

研究思路结论见上方概要

作为女性癌症死亡的第二大原因,乳腺癌已成为全球关注的优先事项。既往基于肿瘤细胞系的研究表明,花生四烯酸(AA)及其代谢产物促进癌症发展。然而,近期基于肿瘤微环境的研究揭示了AA代谢的抗肿瘤作用。因此,有必要重新评估并阐明AA代谢对乳腺癌的影响。

原始数据来自癌症基因组图谱(TCGA)、乳腺癌国际联盟分子分类(METABRIC)和基因表达综合数据库(GEO)。通过生物信息学分析每个样本的AA代谢评分、差异表达基因(DEGs)的富集和免疫浸润。进行Cox回归和最小绝对收缩和选择算子回归以建立AA代谢预后特征。构建了一个用于预测患者生存概率的AA代谢相关列线图。

AA代谢与TCGA-BRCA和METABRIC队列中的良好预后相关。DEGs富集分析表明,高AA代谢组的上调DEGs显著富集于免疫相关通路。高AA代谢组中CD8+ T细胞和活化NK细胞浸润更多。构建了一个用于乳腺癌预后的AA代谢特征(SPINK8、KLRB1、APOD和PIGR)。

展开英文摘要原文

As the second cause of cancer death in women, breast cancer has become a worldwide priority. Previous studies based on tumour cell lines demonstrated that arachidonic acid (AA) and its metabolites promote cancer development. However, recent studies based on the tumour microenvironment revealed the antitumour effect of AA metabolism. Therefore, it is essential to reevaluate and elucidate the effect of AA metabolism on breast cancer.

Raw data were obtained from The Cancer Genome Atlas (TCGA), Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and Gene Expression Omnibus (GEO) databases. The AA metabolic score of each sample, enrichment of differentially expressed genes (DEGs) and immune infiltration were analysed by bioinformatics. Cox regression and least absolute shrinkage and selection operator regression were performed to establish an AA metabolism prognostic signature. An AA metabolism related nomogram for predicting the survival probability of patients was built. RESULT: AA metabolism was related to good prognosis in the TCGA-BRCA and METABRIC cohort. DEGs enrichment suggested that the upregulated DEGs of the high AA metabolism group were significantly enriched in immune-related pathways. The high AA metabolism group was infiltrated with more CD8 + T cells and activated NK cells. An AA metabolic signature (SPINK8, KLRB1, APOD and PIGR) was constructed for breast cancer prognosis.

The study indicated that a high level of AA metabolism may be a biomarker for good prognosis in breast cancer, providing a possible explanation for the discouraging effect of cyclooxygenase inhibitors in cancer therapy. Moreover, a novel AA metabolic prognostic signature was constructed in the study, providing a novel strategy for breast cancer.

论文信息

作者
Li W、Guo X、Chen C、Li J
第一作者单位
Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, 238 Ziyang Road, Wuhan, 430060, Hubei Province, People's Republic of China.China
通讯作者单位
Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, 238 Ziyang Road, Wuhan, 430060, Hubei Province, People's Republic of China. snowy1150219@sina.com.China
期刊
Lipids in health and disease2022 Oct 15
原文标识
PubMed 36243728 · DOI 10.1186/s12944-022-01713-y