Machine learning identifies SRD5A3 as a propionate-related prognostic biomarker in triple-negative breast cancer.

IF 3.9 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
Kelun Pan, Pengjun Qiu, Huikai Liang, Ningning Wan, Zundong Liu, Qiaonan Guo
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Abstract

The increased risk of recurrence and metastasis are obstacles to treating TNBC. Propionate-related genes play an important role in tumor development and immune cell infiltration. The study was to identify the association between propionate-related genes and the prognosis of TNBC patients. Propionate-related genes were collected and analyzed to establish propionate-related gene characteristics. Then, the survival analysis was performed, and the responses to immunotherapies were evaluated. Furthermore, the drug sensitivity of some traditional chemotherapeutic drugs was evaluated. Finally, the hub genes were discovered and validated by in vitro experiments. Based on the five-propionate-related gene signature, TNBC patients were divided into high and low-risk groups. In addition, DEGs between the different risk groups were enriched in the biological activities associated with immunity. TNBC patients in the high-risk groups were suggested to have worse responses to immunotherapies and a poorer prognosis. SRD5A3 was finally found to be a hub gene, and in vitro experiments revealed that silencing SRD5A3 inhibited tumor cell proliferation, invasion, and migration. The five-propionate-related risk model presented novel insights into the efficacy of immunotherapy. It was found that down-regulation of SRD5A3 inhibited the growth and invasion of tumor cells, thereby affecting the prognosis of TNBC.

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机器学习确定SRD5A3是三阴性乳腺癌中丙酸相关的预后生物标志物。
复发和转移的风险增加是治疗TNBC的障碍。丙酸相关基因在肿瘤发生和免疫细胞浸润中起重要作用。该研究旨在确定丙酸相关基因与TNBC患者预后之间的关系。收集并分析丙酸盐相关基因,建立丙酸盐相关基因特征。然后,进行生存分析,并评估对免疫疗法的反应。此外,还评估了一些传统化疗药物的药物敏感性。最后,通过体外实验对中心基因进行了发现和验证。根据5 -丙酸相关基因标记,将TNBC患者分为高危组和低危组。此外,不同风险组之间的deg与免疫相关的生物活性丰富。高危组TNBC患者对免疫治疗反应较差,预后较差。最终发现SRD5A3是一个枢纽基因,体外实验表明,沉默SRD5A3可以抑制肿瘤细胞的增殖、侵袭和迁移。五丙酸相关风险模型对免疫治疗的疗效提出了新的见解。我们发现下调SRD5A3抑制肿瘤细胞的生长和侵袭,从而影响TNBC的预后。
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来源期刊
Scientific Reports
Scientific Reports Natural Science Disciplines-
CiteScore
7.50
自引率
4.30%
发文量
19567
审稿时长
3.9 months
期刊介绍: We publish original research from all areas of the natural sciences, psychology, medicine and engineering. You can learn more about what we publish by browsing our specific scientific subject areas below or explore Scientific Reports by browsing all articles and collections. Scientific Reports has a 2-year impact factor: 4.380 (2021), and is the 6th most-cited journal in the world, with more than 540,000 citations in 2020 (Clarivate Analytics, 2021). •Engineering Engineering covers all aspects of engineering, technology, and applied science. It plays a crucial role in the development of technologies to address some of the world''s biggest challenges, helping to save lives and improve the way we live. •Physical sciences Physical sciences are those academic disciplines that aim to uncover the underlying laws of nature — often written in the language of mathematics. It is a collective term for areas of study including astronomy, chemistry, materials science and physics. •Earth and environmental sciences Earth and environmental sciences cover all aspects of Earth and planetary science and broadly encompass solid Earth processes, surface and atmospheric dynamics, Earth system history, climate and climate change, marine and freshwater systems, and ecology. It also considers the interactions between humans and these systems. •Biological sciences Biological sciences encompass all the divisions of natural sciences examining various aspects of vital processes. The concept includes anatomy, physiology, cell biology, biochemistry and biophysics, and covers all organisms from microorganisms, animals to plants. •Health sciences The health sciences study health, disease and healthcare. This field of study aims to develop knowledge, interventions and technology for use in healthcare to improve the treatment of patients.
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