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低 CDKN1B 表达与 CD8+ T 淋巴细胞减少相关,在机器学习分析中预测乳腺癌不良预后

英文原题:Low CDKN1B Expression Associated with Reduced CD8+ T Lymphocytes Predicts Poor Outcome in Breast Cancer in a Machine Learning Analysis.

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Low CDKN1B Expression Associated with Reduced CD8+ T Lymphocytes Predicts Poor Outcome in Breast Cancer in a Machine Learning Analysis.

PubMed 2023/12/25(内容时间) J Pers Med

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中文摘要

细胞周期蛋白依赖性激酶抑制剂1B(CDKN1B)基因编码p27Kip1蛋白,在调控细胞周期过程和细胞增殖中具有重要作用。其在乳腺癌预后中的作用存在争议。

我们评估了CDKN1B表达在乳腺癌预后中的意义和预测作用。我们根据3794例乳腺癌患者中CDKN1B的表达情况,研究了临床病理因素、生存率、免疫细胞、基因集和预后模型。

我们进行了基因集富集分析(GSEA)、计算机模拟流式细胞术、通路网络分析、梯度提升机(GBM)学习和体外药物筛选。乳腺癌中CDKN1B高表达水平与高淋巴细胞浸润特征评分和CD8+ T细胞增加相关,这两者均与乳腺癌预后改善相关。其与更好的预后相关。CDKN1B表达与T细胞受体信号通路上调和CD8+ T细胞下调的基因集相关。通路网络分析揭示了CDKN1B与蛋白质分解代谢过程正向调控通路之间存在直接联系。

此外,还发现CDKN1B与T细胞受体信号通路之间存在间接联系。在体外药物筛选中,BMS-345541显示出作为靶向CDKN1B治疗药物的疗效,可有效抑制以CDKN1B低表达为特征的乳腺癌细胞生长。将CDKN1B表达纳入GBM模型提高了生存预测的准确性。CDKN1B表达在乳腺癌进展中发挥重要作用,提示靶向CDKN1B可能是治疗乳腺癌的一种有前景的策略。

展开英文摘要原文

The cyclin-dependent kinase inhibitor 1B (CDKN1B) gene, which encodes the p27Kip1 protein, is important in regulating the cell cycle process and cell proliferation. Its role in breast cancer prognosis is controversial.

We evaluated the significance and predictive role of CDKN1B expression in breast cancer prognosis.

We investigated the clinicopathologic factors, survival rates, immune cells, gene sets, and prognostic models according to CDKN1B expression in 3794 breast cancer patients.

We performed gene set enrichment analysis (GSEA), in silico cytometry, pathway network analyses, gradient boosting machine (GBM) learning, and in vitro drug screening. High CDKN1B expression levels in breast cancer correlated with high lymphocyte infiltration signature scores and increased CD8+ T cells, both of which were associated with improved prognosis in breast cancer.

which were associated with a better prognosis. CDKN1B expression was associated with gene sets for the upregulation of T-cell receptor signaling pathways and downregulation of CD8+ T cells. Pathway network analysis revealed a direct link between CDKN1B and the pathway involved in the positive regulation of the protein catabolic process pathway.

In addition, an indirect link was identified between CDKN1B and the T-cell receptor signaling pathway. In in vitro drug screening, BMS-345541 demonstrated efficacy as a therapeutic targeting of CDKN1B, effectively impeding the growth of breast cancer cells characterized by low CDKN1B expression. The inclusion of CDKN1B expression in GBM models increased the accuracy of survival predictions. CDKN1B expression plays a significant role in breast cancer progression, implying that targeting CDKN1B might be a promising strategy for treating breast cancer.

论文信息

作者
Kim HS、Noh YK、Min KW、Kim DH
第一作者单位
Division of Breast Surgery, Department of Surgery, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri 15588, Republic of Korea.South Korea
通讯作者单位
Department of Pathology, Kangbuk Samsung Hospital, School of Medicine, Sungkyunkwan University, 29 Saemunanro, Seoul 03181, Republic of Korea.South Korea
期刊
Journal of personalized medicine2023 Dec 25
原文标识
PubMed 38248731 · DOI 10.3390/jpm14010030