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糖基转移酶相关亚型的综合分析揭示了乳腺癌中的预后基因和免疫景观

英文原题:Comprehensive analysis of glycosyl transferase-related subtypes reveals prognostic genes and immune landscape in breast cancer.

查看英文原题

Comprehensive analysis of glycosyl transferase-related subtypes reveals prognostic genes and immune landscape in breast cancer.

PubMed 2025/08/01(内容时间) Medicine (Baltimore) Q2 · IF 2(JCR 2025)

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中文摘要

乳腺癌(BC)表现出广泛的异质性,使个体化治疗复杂化。糖基转移酶(GTs)是癌症治疗的潜在生物标志物。在癌症基因组图谱乳腺癌队列中对GT相关基因(GTRGs)进行了共识聚类。分析了临床特征、生存结局和分子通路。评估了肿瘤微环境的差异。机器学习技术(Lasso、随机森林、XGBoost)识别了核心GTRGs。构建了整合核心GTRGs和临床特征的预后列线图。

最后进行了细胞验证实验。识别出两个亚型(C1和C2),C1显示出比C2更好的生存(P = .0029)。C1具有更高的CD8 T细胞和活化NK细胞,而巨噬细胞比例较低。

此外,GTs相关的mTORC1和PI3K/AKT/mTOR通路被抑制,而p53、Wnt/β-Catenin和Notch通路被激活。识别出4个核心GTRGs(ATP5F1B、CS、EPB41L4B和LIMCH1)。这些基因的高表达与较差预后相关。列线图展示了该核心GTRGs预测1年、3年和5年总生存期的高准确性。

此外,4个核心基因的表达水平在BC细胞系MDA-MB-415中较高,CS敲低显著抑制了MDA-MB-415细胞的增殖和迁移。BC中的GT相关亚型与不同的生存结局和免疫景观相关。核心GTRGs是有价值的预后标志物,有助于个体化治疗策略。

展开英文摘要原文

Breast cancer (BC) exhibits extensive heterogeneity, complicating personalized treatment. Glycosyl transferases (GTs) are potential biomarkers for cancer treatment. Consensus clustering was performed on GT-related genes (GTRGs) in the The Cancer Genome Atlas Breast Cancer cohort. Clinical characteristics, survival outcomes, and molecular pathways were analyzed. Differences in the tumor microenvironment were assessed.

Machine learning techniques (Lasso, random forest, XGBoost) identified hub GTRGs. A prognostic nomogram was constructed integrating hub GTRGs and clinical features. The cell validation experiments were finally performed. Two subtypes (C1 and C2) were identified, and C1 showed better survival than C2 (P = . 0029). C1 had higher CD8 T cells and activated NK cells, while macrophage fractions were lower.

In addition, GTs-related mTORC1 and PI3K/AKT/mTOR pathways were suppressed, whereas p53, Wnt/β-Catenin, and Notch pathways were activated. 4 hub GTRGs (ATP5F1B, CS, EPB41L4B, and LIMCH1) were identified. High expression of these genes correlated with poorer prognosis. The nomogram demonstrated high accuracy of this hub GTRGs for predicting 1-, 3-, and 5-year overall survival.

Additionally, expression levels of 4 hub genes were higher in the BC cell line MDA-MB-415, and CS knockdown significantly inhibited the proliferation and migration of MDA-MB-415 cells. GT-related subtypes in BC are linked to distinct survival outcomes and immune landscapes. Hub GTRGs are valuable prognostic markers, aiding personalized treatment strategies.

论文信息

作者
Qiu JL、Chen JN、Lu JL
单位
Department of Breast Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.China
期刊
Medicine2025 Aug 1
原文标识
PubMed 40760614 · DOI 10.1097/MD.0000000000043523