Characterizing the role of SLC3A2 in the molecular landscape and immune microenvironment across human tumors.
Characterizing the role of SLC3A2 in the molecular landscape and immune microenvironment across human tumors.
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DOI：
10.3389/fmolb.2022.961410
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发表时间：
2022
影响因子：
5
通讯作者：
中科院分区：
文献类型：
--
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背景资料：在人类肿瘤中诱导铁凋亡已经成为改善患者预后的潜在策略，即使在那些具有化疗抗性的患者中也是如此。xCT复合物是诱导铁凋亡的主要靶点，由SLC 7A 11和SLC 3A 2组成。近年来，SLC 7A 11在癌症中的作用得到了广泛的研究。然而，针对其伴侣SLC 3A 2的相关研究仍然很少。 方法：采用大规模转录组、单细胞测序和免疫组化方法分析SLC 3A 2的表达分布。结合临床结果分析SLC 3A 2表达与患者预后的关系。免疫细胞浸润通过多重去卷积算法估计。DEPMAP法检测SLC 3A 2对肿瘤细胞增殖和耐药性的影响。 结果：SLC 3A 2表达上调可能对低级别胶质瘤和急性髓系白血病等多种肿瘤的生存产生不利影响。SLC 3A 2的表达对于多种细胞系的增殖是必不可少的，特别是对于ESO 51（食管癌细胞系）。此外，SLC 3A 2表达水平与癌症中免疫微环境的重塑以及一些免疫检查点（如PD-1和PD-L1）相关，这些免疫检查点是许多不同癌症的潜在治疗靶点。 结论：本研究系统阐明了SLC 3A 2在肿瘤患者生存和潜在免疫应答中的作用。SLC 3A 2调控抗肿瘤免疫的分子机制尚不清楚，这是目前研究的主要局限。未来对生物学机制的研究可以进一步帮助癌症患者的靶向治疗。
Background: Inducing ferroptosis in human tumors has become a potential strategy to improve the prognosis of patients, even in those with chemotherapeutic resistance. The xCT complex is a major target for ferroptosis induction, constituted by SLC7A11 and SLC3A2. The role of SLC7A11 in cancer has been widely studied in recent years. However, related research studies for its partner SLC3A2 are still rare. Methods: Bulk transcriptome, single-cell sequencing, and immunohistochemical staining were analyzed to explore the expression distribution of SLC3A2. Clinical outcomes were referred to uncover the relationship between SLC3A2 expression and patients’ prognosis. Immune cell infiltration was estimated by multiple deconvolution algorithms. The effect of SLC3A2 on the proliferation and drug resistance of cancer cell lines was evaluated by DEPMAP. Results: Upregulated SLC3A2 may have an adverse effect on the survival of multiple cancers such as lower-grade glioma and acute myeloid leukemia. SLC3A2 expression is indispensable for multiple cell lines’ proliferation, especially for ESO51 (a cell line for esophageal cancer). In addition, SLC3A2 expression level was related to the remodeling of the immune microenvironment in cancers and some immune checkpoints such as PD-1 and PD-L1, which were potential therapeutic targets in many distinct cancers. Conclusion: Our study systematically elucidated the role of SLC3A2 in the survival of cancer patients and the potential immunotherapeutic response. Few molecular mechanisms by which SLC3A2 regulates anti-tumor immunity have been clarified in the present study, which is the main limitation. Future research into the biological mechanism could further help with targeted treatment for cancer patients.
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影响因子：
7.7
作者：
Racle J;de Jonge K;Baumgaertner P;Speiser DE;Gfeller D
通讯作者：
Gfeller D
影响因子：
--
作者：
Wang S;Han H;Hu Y;Yang W;Lv Y;Wang L;Zhang L;Ji J
通讯作者：
Ji J
影响因子：
9.7
作者：
Liu, Mengrui;Song, Wantong;Huang, Leaf
通讯作者：
Huang, Leaf
影响因子：
3.3
作者：
Liang, Jiayu;Sun, Zhida
通讯作者：
Sun, Zhida
影响因子：
5.7
作者：
Shin, Dong Hoon;Jo, Jeong Yeon;Han, Ji-Youn
通讯作者：
Han, Ji-Youn