PDF(Pubmed)
Abstract：
Upregulation of metabolism-related gene cytidine triphosphate synthase 1 (CTPS1) is associated with poor prognosis in multiple myeloma (MM). However, its role in MM remains unclear. In this study, bioinformatics analysis revealed significant differences in CTPS1 expression levels among various plasma cell malignancies. The patients with high CTPS1 expression had poor overall survival, progression-free survival, and event-free survival. CTPS1 was significantly correlated with sex, albumin, β2 microglobulin, lactate dehydrogenase, and advanced disease. In vitro experiments demonstrated that CTPS1-overexpressing (CTPS1-OE) cells proliferated faster than CTPS1-short hairpin RNA (CTPS1-sh) cells. NRG-SGM3 mice showed significantly accelerated tumor growth in the CTPS1-OE group. CTPS1-OE decreased sensitivity to bortezomib, whereas CTPS1-sh increased sensitivity to bortezomib in MM cell lines. Mechanistically, CTPS1 was primarily involved in metabolism processes. Additionally, CTPS1 was closely related to several co-expressed genes such as MYC and the bone marrow immune microenvironment. In conclusion, CTPS1 is a significant prognostic biomarker for patients with MM, suggesting a potential therapeutic target.
摘要：
代谢相关基因三磷酸胞苷合酶1（CTPS1）上调与多发性骨髓瘤（MM）预后不良相关。然而,其在MM中的作用尚不清楚。在这项研究中,生物信息学分析显示,各种浆细胞恶性肿瘤中CTPS1表达水平存在显著差异.CTPS1高表达的患者总生存期较差,无进展生存期,和无事件生存。CTPS1与性别显著相关,白蛋白,β2微球蛋白，乳酸脱氢酶,和晚期疾病。体外实验表明，CTPS1过表达（CTPS1-OE）细胞比CTPS1短发夹RNA（CTPS1-sh）细胞增殖更快。NRG-SGM3小鼠在CTPS1-OE组中显示出显著加速的肿瘤生长。CTPS1-OE降低了对硼替佐米的敏感性，而CTPS1-sh增加MM细胞系对硼替佐米的敏感性。机械上,CTPS1主要参与代谢过程。此外,CTPS1与MYC和骨髓免疫微环境等共表达基因密切相关。总之,CTPS1是MM患者的重要预后生物标志物，提示潜在的治疗靶点。
