研究动态
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SLC3A2 升高与胶质瘤预后不良和恶性程度增强相关。

Elevated SLC3A2 associated with poor prognosis and enhanced malignancy in gliomas.

发表日期:2024 Jul 09
作者: Yuheng Xu, Wanqi Weng, Yuhao Weng, Danmin Chen, Ziwen Zheng, Zexian Fan, Chengxiang Peng, Yuanyi Xiong, Xiao Pang, Guobin Cao, Yezhong Wang, Quan Mo, Zhaotao Wang, Shizhen Zhang
来源: Brain Structure & Function

摘要:

SLC3A2(一种与二硫下垂有关的基因)在神经胶质瘤中的作用尚未得到表征。本研究旨在阐明SLC3A2的预后价值及其对胶质瘤的影响。我们使用公开数据库和我们的临床神经胶质瘤样本并依靠 Meta 和 Cox 回归分析方法评估了 SLC3A2 的表达及其在神经胶质瘤中的预后重要性。进行功能富集分析以探索 SLC3A2 的功能。使用 CIBERSORT、ssGSEA 和单细胞测序数据评估免疫浸润。此外,还确定了肿瘤免疫功能障碍和排斥(TIDE)和上皮间质转化评分。在体外利用 CCK8、集落形成、迁移和侵袭测定,并在体内采用原位神经胶质瘤异种移植模型,以研究 SLC3A2 在神经胶质瘤中的作用。生物信息学分析表明,SLC3A2 高表达与不良临床病理特征和不良患者预后相关。 SLC3A2上调通过改变免疫细胞浸润(尤其是巨噬细胞)以及肿瘤迁移和侵袭来影响肿瘤微环境。 SLC3A2表达与免疫治疗指标呈正相关,包括免疫检查点和TIDE。通过 Cox 回归分析,SLC3A2 升高被揭示为神经胶质瘤预后不良的独立风险因素。体外实验表明,SLC3A2 表达减少会降低细胞增殖、迁移和侵袭。在体内,SLC3A2 的敲低导致荷瘤小鼠的肿瘤体积减小并延长了生存期。因此,SLC3A2 是一种预后生物标志物,与神经胶质瘤的免疫浸润相关。© 2024。作者。
The role of SLC3A2, a gene implicated in disulfidptosis, has not been characterized in gliomas. This study aims to clarify the prognostic value of SLC3A2 and its influence on glioma. We evaluated the expression of SLC3A2 and its prognostic importance in gliomas using publicly accessible databases and our clinical glioma samples and with reliance on Meta and Cox regression analysis approaches. Functional enrichment analyses were performed to explore SLC3A2's function. Immune infiltration was evaluated using CIBERSORT, ssGSEA, and single-cell sequencing data. Additionally, Tumor immune dysfunction and exclusion (TIDE) and epithelial-mesenchymal transition scores were determined. CCK8, colony formation, migration, and invasion assays were utilized in vitro, and an orthotopic glioma xenograft model was employed in vivo, to investigate the role of SLC3A2 in gliomas. Bioinformatics analyses indicated high SLC3A2 expression correlates with adverse clinicopathological features and poor patient prognosis. Upregulated SLC3A2 influenced the tumor microenvironment by altering immune cell infiltration, particularly of macrophages, and tumor migration and invasion. SLC3A2 expression positively correlated with immune therapy indicators, including immune checkpoints and TIDE. Elevated SLC3A2 was revealed as an independent risk element for poor glioma prognosis through Cox regression analyses. In vitro experiments showed that reduced SLC3A2 expression decreased cell proliferation, migration, and invasion. In vivo, knockdown of SLC3A2 led to a reduction in tumor volume and prolonged survival in tumor-bearing mice. Therefore, SLC3A2 is a prognostic biomarker and associated with immune infiltration in gliomas.© 2024. The Author(s).