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细胞死亡相关生物标志物SLC2A1在泛癌的预后预测和免疫治疗疗效评估中具有重要作用。

Cell death-related biomarker SLC2A1 has a significant role in prognosis prediction and immunotherapy efficacy evaluation in pan-cancer.

作者信息

Wang Yuhang, Wang Kai, Zhang Han, Jia Xiaoteng, Li Xin, Sun Shuai, Sun Daqiang

机构信息

Graduate School, Tianjin Medical University, Tianjin, China.

Clinical School of Thoracic, Tianjin Medical University, Tianjin, China.

出版信息

Front Genet. 2023 Jan 11;13:1068462. doi: 10.3389/fgene.2022.1068462. eCollection 2022.

Abstract

SLC2A1, a member of the SLC transporter family, is involved in a variety of cell death modalities and has been found to be associated with the prognosis and immune microenvironment of a variety of tumors. However, there is a lack of systematic and comprehensive studies on the role of SLC2A1 in pan-cancer. The mRNA, promoter methylation, and protein expression levels of SLC2A1 in pan-cancer were comprehensively evaluated using GEPIA2.0, TIMER2.0, and UALCAN databases. UCSCXenaShiny based on the cancer genomic atlas pan-cancer data and GEPIA2.0 database were used to assess the prognostic significance of SLC2A1 in pan-cancer. Genetic alterations in were also evaluated using cBioPortal. The relevance of SLC2A1 to immune infiltrating cells in pan-cancer was evaluated using the XCELL algorithm in combination with the TIMER2.0 database. The correlation of SLC2A1 with the efficacy of immune checkpoint blocker (ICB) therapy was evaluated using the tumor immune dysfunction and exclusion (TIDE) score. The correlation of SLC2A1 with numerous immune-related markers was also evaluated using the TISIDB database. The correlation of SLC2A1 with tumor biological function was evaluated at the single-cell level using the CancerSEA database. Finally, the biological function of SLC2A1 was comprehensively evaluated using gene set enrichment analysis (GSEA) and protein interaction networks. SLC2A1 expression is aberrant in a variety of tumors and is strongly associated with the prognosis of several cancers. SLC2A1 is significantly associated with a variety of immune infiltrating cells including CD8 T cells, myeloid-derived suppressor cells and macrophages in a variety of tumors. Meanwhile, the expression of SLC2A1 significantly correlated with multiple immune-related markers. In addition, SLC2A1 can also predict the effect of immune checkpoint blocker therapy in some tumors. In a functional analysis, SLC2A1 was significantly associated with hypoxia, epithelial-mesenchymal transition, mTORC1 signaling, and multiple metabolic pathways in pan-cancer. Our study systematically and comprehensively summarizes the prognostic significance and immune-related role of SLC2A1 in pan-cancer and reveals the potential mechanism of SLC2A1 in regulating the tumor microenvironment and tumor behavior, providing a new effective pan-applicable biomarker for prognostic prediction and the evaluation of immunotherapeutic strategies for tumors.

摘要

SLC2A1是SLC转运蛋白家族的成员之一,参与多种细胞死亡方式,并且已发现其与多种肿瘤的预后和免疫微环境相关。然而,目前缺乏关于SLC2A1在泛癌中作用的系统全面研究。利用GEPIA2.0、TIMER2.0和UALCAN数据库综合评估了SLC2A1在泛癌中的mRNA、启动子甲基化和蛋白表达水平。基于癌症基因组图谱泛癌数据和GEPIA2.0数据库的UCSCXenaShiny用于评估SLC2A1在泛癌中的预后意义。还使用cBioPortal评估了基因改变情况。利用XCELL算法结合TIMER2.0数据库评估了SLC2A1与泛癌中免疫浸润细胞的相关性。利用肿瘤免疫功能障碍和排除(TIDE)评分评估了SLC2A1与免疫检查点阻断剂(ICB)治疗疗效的相关性。还使用TISIDB数据库评估了SLC2A1与众多免疫相关标志物的相关性。利用CancerSEA数据库在单细胞水平评估了SLC2A1与肿瘤生物学功能的相关性。最后,使用基因集富集分析(GSEA)和蛋白质相互作用网络全面评估了SLC2A1的生物学功能。SLC2A1在多种肿瘤中表达异常,且与多种癌症的预后密切相关。SLC2A1在多种肿瘤中与包括CD8 T细胞、髓源性抑制细胞和巨噬细胞在内的多种免疫浸润细胞显著相关。同时,SLC2A1的表达与多种免疫相关标志物显著相关。此外,SLC2A1在某些肿瘤中还可以预测免疫检查点阻断剂治疗的效果。在功能分析中,SLC2A1在泛癌中与缺氧、上皮-间质转化、mTORC1信号传导和多种代谢途径显著相关。我们的研究系统全面地总结了SLC2A1在泛癌中的预后意义和免疫相关作用,揭示了SLC2A1调节肿瘤微环境和肿瘤行为的潜在机制,为肿瘤的预后预测和免疫治疗策略评估提供了一种新的有效且广泛适用的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cebd/9873976/0be58bf2b101/fgene-13-1068462-g001.jpg

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