Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi 214062, Jiangsu, China; Laboratory of Cancer Epigenetics, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, Jiangsu, China.
Department of Digestive Center, Affiliated Hospital of Jiangnan University, Wuxi 214062, Jiangsu, China.
Pathol Res Pract. 2021 Aug;224:153525. doi: 10.1016/j.prp.2021.153525. Epub 2021 Jun 12.
Although SLC1A5 has been reported to be closely associated with some cancer types, a comprehensive and systematic assessment of SLC1A5 across human cancers is lacking. Thus, Pan-cancer analysis of SLC1A5 was performed across 30 types of human cancers in this study. We examined mRNA expression, protein expression, copy number variation (CNV), DNA methylation, clinical relevance, cell functions, drug response and total immune infiltrates of SLC1A5 in more than 9000 patients across 30 human cancer types from The Cancer Genome Atlas (TCGA) dataset. Additionally, nine independent Gene Expression Omnibus datasets, more than 800 cancer cell lines from the Cancer Cell Line Encyclopedia dataset and the Project Achilles dataset were used to validate our findings in the TCGA dataset. Landscapes of SLC1A5 were established across multiple cancers. We showed that SLC1A5 is upregulated in multiple cancers, particularly in digestive and respiratory system cancers. SLC1A5 upregulation may be driven by CNV gain and DNA hypomethylation in human cancers. Furthermore, SLC1A5 overexpression is associated with tumor progression and poor survival in multiple cancers. Moreover, we systematically explored the potential effects of SLC1A5 expression on cell functions and drug response in human cancers. SLC1A5 knockdown showed significant proliferation-inhibiting effects in most human cancer types, especially in the digestive system and KRAS-mutant cancers. SLC1A5 expression is associated with proliferation activities of KRAS-mutant cancer cell lines and drug response of many anti-cancer drugs. Finally, we demonstrated that SLC1A5-realted tumor immune microenvironment characteristics showed strong heterogeneity in human cancers. Taken together, our findings highlight the important roles of SLC1A5 in tumorigenesis, progression, prognosis and therapy.
虽然 SLC1A5 已被报道与一些癌症类型密切相关，但对其在人类癌症中的全面系统评估仍然缺乏。因此，本研究对 30 种人类癌症进行了 SLC1A5 的泛癌症分析。我们检查了 SLC1A5 在超过 9000 名来自癌症基因组图谱 (TCGA) 数据集的 30 种人类癌症患者中的 mRNA 表达、蛋白表达、拷贝数变异 (CNV)、DNA 甲基化、临床相关性、细胞功能、药物反应和总免疫浸润。此外，还使用了来自基因表达综合数据库 (GEO) 的 9 个独立数据集、来自癌症细胞系百科全书数据库和 Project Achilles 数据库的超过 800 个癌症细胞系，以验证我们在 TCGA 数据集中的发现。建立了 SLC1A5 在多种癌症中的图谱。我们表明，SLC1A5 在多种癌症中上调，尤其是在消化系统和呼吸系统癌症中。人类癌症中 SLC1A5 的上调可能是由 CNV 增益和 DNA 低甲基化驱动的。此外，SLC1A5 的过表达与多种癌症的肿瘤进展和不良预后相关。此外，我们系统地探索了 SLC1A5 表达对人类癌症中细胞功能和药物反应的潜在影响。SLC1A5 敲低在大多数人类癌症类型中表现出显著的增殖抑制作用，尤其是在消化系统和 KRAS 突变型癌症中。SLC1A5 的表达与 KRAS 突变型癌细胞系的增殖活性和许多抗癌药物的药物反应相关。最后，我们证明 SLC1A5 相关的肿瘤免疫微环境特征在人类癌症中表现出很强的异质性。总之，我们的研究结果强调了 SLC1A5 在肿瘤发生、进展、预后和治疗中的重要作用。
