Department of Pathology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Gyeonggi-do, Republic of Korea.
Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
PLoS One. 2021 Mar 18;16(3):e0245075. doi: 10.1371/journal.pone.0245075. eCollection 2021.
High expression of glucose transporter family members, which augment glucose uptake and glycolytic flux, has been shown to play a pivotal role in the proliferation and survival of tumor cells, contributing to the energy supply, biosynthesis and homeostasis of cancer cells. Among the many members, solute carrier family 2 member 1 (SLC2A1) encodes a glucose transporter, GLUT1, that is critical in the metabolism of glucose, which is an energy source for cell growth that contributes to cancer progression and development. The aim of this study was to analyze the survival and genetic changes/immune profiles in patients with gastric cancer with high SLC2A1 expression and to provide treatment for improving prognosis. This study investigated the clinicopathologic parameters, the proportion of immune cells and gene sets affecting SLC2A1 expression in 279 and 415 patients with gastric cancer from the Eulji Hospital cohort and The Cancer Genome Atlas, respectively. We assessed the response to conventional chemotherapy drugs, including fluorouracil, a compound of fluoropyrimidine S-1, oxaliplatin, and all-trans-retinoic acid (ATRA), in gastric cancer cell lines with high SLC2A1 expression. High SLC2A1 expression was associated with poor prognosis, cancer cell proliferation, decreased immune cells, including CD8 T cells and B cells, and a low prognostic nutrition index, representing body nutrition-related status. In pathway network analysis, SLC2A1 was indirectly linked to the retinoic signaling pathway and negatively regulated immune cells/receptors. In the drug response analysis, the drug ATRA inhibited gastric cancer cell lines with high SLC2A1 expression. Treatment involving the use of SLC2A1 could contribute to better clinical management/research for patients with gastric cancer.
高表达的葡萄糖转运体家族成员（可增加葡萄糖摄取和糖酵解通量）在肿瘤细胞的增殖和存活中发挥关键作用，有助于为癌细胞提供能量供应、生物合成和内环境稳定。在众多成员中，溶质载体家族 2 成员 1（SLC2A1）编码葡萄糖转运蛋白 GLUT1，在葡萄糖代谢中至关重要，葡萄糖是细胞生长的能量来源，有助于癌症的进展和发展。本研究旨在分析高 SLC2A1 表达的胃癌患者的生存和遗传变化/免疫特征，并提供改善预后的治疗方法。本研究分别从 Eulji 医院队列和癌症基因组图谱中调查了 279 名和 415 名胃癌患者的临床病理参数、影响 SLC2A1 表达的免疫细胞比例和基因集，并评估了包括氟尿嘧啶、氟嘧啶 S-1 化合物、奥沙利铂和全反式维甲酸（ATRA）在内的常规化疗药物在高 SLC2A1 表达的胃癌细胞系中的反应。高 SLC2A1 表达与预后不良、癌细胞增殖、减少的免疫细胞（包括 CD8 T 细胞和 B 细胞）和低预后营养指数（代表与身体营养相关的状态）相关。在途径网络分析中，SLC2A1 与视黄酸信号通路间接相关，并负调控免疫细胞/受体。在药物反应分析中，药物 ATRA 抑制了高 SLC2A1 表达的胃癌细胞系。使用 SLC2A1 的治疗方法可能有助于改善胃癌患者的临床管理/研究。
