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去泛素化酶相关特征可预测乳腺癌的预后和免疫治疗反应。

The deubiquitinating enzymes-related signature predicts the prognosis and immunotherapy response in breast cancer.

机构信息

Department of General Surgery, Xiangtan Central Hospital, Xiangtan 410000, Hunan, P.R. China.

Department of Pathology, Xiangtan Central Hospital, Xiangtan 410000, Hunan, P.R. China.

出版信息

Aging (Albany NY). 2024 Jul 9;16(15):11553-11567. doi: 10.18632/aging.206010.

Abstract

BACKGROUND

Breast cancer is a prevalent disease that has a dismal prognosis for patients and a bad outlook for treatments. Ubiquitination is a reversible biological process that regulates protein production and degradation, as well as plays a vital role in protein transport, localization, and biological activity.

METHODS

We obtained the breast cancer patient sample data and used a machine learning technique to create a novel index called Deubiquitinating enzyme related index (DUBRI) by gathering genes associated to deubiquitinating enzymes. Based on DUBRI, we systematically analyze patients' prognosis, clinical characteristics, tumor immune microenvironment, chemotherapy response and immunotherapy response. Finally, the function of OTUB2 was explored in breast cancer cells.

RESULTS

DUBRI, which consists of five deubiquitinating enzyme genes (OTUB2, USP41, MINDY2, YOD1, and PSMD7), is a reliable predictor of survival in breast cancer patients. We found that the high DUBRI group presented higher levels of immune cell infiltration. We performed molecular docking prediction of core target proteins in deubiquitinating enzymes. experiments verified that knockdown of OTUB2 could inhibit the proliferation and migration of breast cancer.

CONCLUSIONS

The DUBRI discovered in this research may effectively evaluate the outlook of breast cancer patients and identify groups of patients who would gain advantages from immunotherapy, offering vital knowledge for the future targeted treatment of breast cancer patients.

摘要

背景

乳腺癌是一种常见疾病,患者预后不良,治疗效果不佳。泛素化是一种可逆的生物过程,可调节蛋白质的产生和降解,在蛋白质运输、定位和生物活性中起着至关重要的作用。

方法

我们获得了乳腺癌患者的样本数据,并通过收集与去泛素化酶相关的基因,使用机器学习技术创建了一个新的指标,称为去泛素化酶相关指数(DUBRI)。基于 DUBRI,我们系统地分析了患者的预后、临床特征、肿瘤免疫微环境、化疗反应和免疫治疗反应。最后,在乳腺癌细胞中探索了 OTUB2 的功能。

结果

DUBRI 由五个去泛素化酶基因(OTUB2、USP41、MINDY2、YOD1 和 PSMD7)组成,是乳腺癌患者生存的可靠预测指标。我们发现高 DUBRI 组的免疫细胞浸润水平更高。我们进行了去泛素化酶核心靶蛋白的分子对接预测。实验验证了敲低 OTUB2 可以抑制乳腺癌的增殖和迁移。

结论

本研究发现的 DUBRI 可能能够有效地评估乳腺癌患者的预后,并确定从免疫治疗中获益的患者群体,为未来乳腺癌患者的靶向治疗提供重要知识。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fd1/11346791/1bd2764986d2/aging-16-206010-g001.jpg

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