研究动态
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SLC1A5是与铁死亡和肿瘤微环境相关的一种新生物标志物:一项全癌分析。

SLC1A5 is a novel biomarker associated with ferroptosis and the tumor microenvironment: a pancancer analysis.

发表日期:2023 Aug 10
作者: Peng Chen, YongAn Jiang, JiaWei Liang, JiaHong Cai, Yi Zhuo, HengYi Fan, RaoRao Yuan, ShiQi Cheng, Yan Zhang
来源: Immunity & Ageing

摘要:

溶质载体家族1成员5(SLC1A5)是溶质载体(SLC)超家族的一员,在肿瘤中作为谷氨酰胺进入细胞的关键转运蛋白发挥着重要作用。然而,SLC1A5在免疫调控中的作用以及其与肿瘤微环境中的免疫细胞浸润之间的关系尚未阐明,而SLC1A5与铁死亡关系的报道也非常少。因此,我们全面分析了SLC1A5在癌症中的表达水平,并将其与正常组织中的表达水平进行了比较。然后,通过单细胞分析、基因集富集分析(GSEA)和肿瘤免疫估计资源(TIMER),分析了SLC1A5表达与肿瘤免疫微环境之间的关系。接下来,评估了SLC1A5表达水平与免疫治疗反应、免疫调节剂表达、肿瘤突变负荷(TMB)和微卫星不稳定性(MSI)之间的相关性。最后,体外实验验证了SLC1A5参与胶质瘤细胞铁死亡调节肿瘤进展的作用。我们的结果表明,SLC1A5在大多数癌症类型中异常表达,并与预后密切相关。GSEA结果显示,SLC1A5参与免疫激活过程,并与不同癌症类型的不同免疫细胞浸润水平密切相关。进一步调查发现,在胶质瘤中,SLC1A5是铁死亡的抑制剂,SLC1A5沉默抑制了体外胶质瘤细胞的增殖和迁移。总之,我们进行了SLC1A5的全癌症分析,证明了其作为癌症患者预后生物标志物的作用,并探讨了其潜在的生物学功能。
Solute carrier family 1 member 5 (SLC1A5) is a member of the solute carrier (SLC) superfamily of transporters and plays an important role in tumors as a key transporter of glutamine into cells. However, the relationship between SLC1A5, which is involved in immune regulation, and immune cell infiltration in the tumor microenvironment has not been elucidated, and the relationship between SLC1A5 and ferroptosis is rarely reported. Therefore, we comprehensively analyzed the expression level of SLC1A5 across cancers and compared it with that in normal tissues. Then, the relationship between SLC1A5 expression and the tumor immune microenvironment was analyzed by single-cell analysis, gene set enrichment analysis (GSEA), and Tumor Immune Estimation Resource (TIMER). Next, the correlations of the SLC1A5 expression level with immunotherapy response, immunomodulator expression, tumor mutation burden (TMB) and microsatellite instability (MSI) were evaluated. Finally, in vitro experiments verified that SLC1A5 participates in ferroptosis of glioma cells to regulate tumor progression. Our results indicated that SLC1A5 is aberrantly expressed in most cancer types and closely associated with prognosis. The GSEA results showed that SLC1A5 is involved in immune activation processes and closely related to the infiltration levels of different immune cells in different cancer types. Upon further investigation, we found that SLC1A5 is a suppressor of ferroptosis in glioma, and SLC1A5 knockdown inhibited the proliferation and migration of glioma cells in vitro. In conclusion, we conducted a pancancer analysis of SLC1A5, demonstrated its role as a prognostic biomarker in cancer patients and explored its potential biological functions.