文章：

含三结构域蛋白2，一种与谷氨酰胺代谢相关的蛋白，可预测三阴性乳腺癌化疗患者的不良预后

Tripartite Motif-Containing 2, a Glutamine Metabolism-Associated Protein, Predicts Poor Patient Outcome in Triple-Negative Breast Cancer Treated with Chemotherapy

原文发布日期：21 May 2024

DOI: 10.3390/cancers16111949

类型: Article

开放获取: 是

英文摘要：

Background: Breast cancer (BC) remains heterogeneous in terms of prognosis and response to treatment. Metabolic reprogramming is a critical part of oncogenesis and a potential therapeutic target. Glutaminase (GLS), which generates glutamate from glutamine, plays a role in triple-negative breast cancer (TNBC). However, targeting GLS directly may be difficult, as it is essential for normal cell function. This study aimed to determine potential targets in BC associated with glutamine metabolism and evaluate their prognostic value in BC. Methods: The iNET model was used to identify genes in BC that are associated withGLSusing RNA-sequencing data. The prognostic significance of tripartite motif-containing 2 (TRIM2) mRNA was assessed in BC transcriptomic data (n= 16,575), and TRIM2 protein expression was evaluated using immunohistochemistry (n= 749) in patients with early-stage invasive breast cancer with long-term follow-up. The associations between TRIM2 expression and clinicopathological features and patient outcomes were evaluated. Results: Pathway analysis identifiedTRIM2expression as an important gene co-expressed with highGLSexpression in BC. HighTRIM2mRNA and TRIM2 protein expression were associated with TNBC (p< 0.01). TRIM2 was a predictor of poor distant metastasis-free survival (DMFS) in TNBC (p< 0.01), and this was independent of established prognostic factors (p< 0.05), particularly in those who received chemotherapy (p< 0.05). In addition, TRIM2 was a predictor of shorter DMFS in TNBC treated with chemotherapy (p< 0.01). Conclusions: This study provides evidence of an association between TRIM2 and poor patient outcomes in TNBC, especially those treated with chemotherapy. The molecular mechanisms and functional behaviour of TRIM2 and the functional link with GLS in BC warrant further exploration using in vitro models.

摘要翻译： 

背景：乳腺癌在预后和治疗反应方面仍存在异质性。代谢重编程是肿瘤发生的关键环节，也是潜在的治疗靶点。谷氨酰胺酶（GLS）能将谷氨酰胺转化为谷氨酸，在三阴性乳腺癌（TNBC）中发挥重要作用。然而，直接靶向GLS可能存在困难，因为其对正常细胞功能至关重要。本研究旨在确定与谷氨酰胺代谢相关的乳腺癌潜在靶点，并评估其在乳腺癌中的预后价值。 方法：本研究利用iNET模型，基于RNA测序数据识别乳腺癌中与GLS相关的基因。在乳腺癌转录组数据（n=16,575）中评估了三结构域蛋白2（TRIM2）mRNA的预后意义，并通过免疫组织化学方法（n=749）评估了具有长期随访的早期浸润性乳腺癌患者的TRIM2蛋白表达水平。分析了TRIM2表达与临床病理特征及患者预后的关联。 结果：通路分析确定TRIM2是乳腺癌中与高GLS表达共表达的重要基因。高TRIM2 mRNA和TRIM2蛋白表达均与TNBC相关（p<0.01）。TRIM2是TNBC患者远处转移无病生存期（DMFS）不良的预测因子（p<0.01），且独立于已知的预后因素（p<0.05），在接受化疗的患者中尤为显著（p<0.05）。此外，TRIM2是接受化疗的TNBC患者DMFS缩短的预测指标（p<0.01）。 结论：本研究证实了TRIM2与TNBC患者不良预后（尤其是接受化疗者）之间的关联。TRIM2的分子机制、功能特性及其与GLS在乳腺癌中的功能联系，值得通过体外模型进一步探索。

原文链接：

Tripartite Motif-Containing 2, a Glutamine Metabolism-Associated Protein, Predicts Poor Patient Outcome in Triple-Negative Breast Cancer Treated with Chemotherapy