Tolwani Angela, Matusiak Magdalena, Bui Nam, Forgó Erna, Varma Sushama, Baratto Lucia, Iagaru Andrei, Lazar Alexander J, van de Rijn Matt, Przybyl Joanna
Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
NPJ Genom Med. 2021 May 3;6(1):30. doi: 10.1038/s41525-021-00193-w.
Metabolic reprogramming of tumor cells and the increase of glucose uptake is one of the hallmarks of cancer. In order to identify metabolic pathways activated in leiomyosarcoma (LMS), we analyzed transcriptomic profiles of distinct subtypes of LMS in several datasets. Primary, recurrent and metastatic tumors in the subtype 2 of LMS showed consistent enrichment of genes involved in hexosamine biosynthesis pathway (HBP). We demonstrated that glutamine-fructose-6-phosphate transaminase 2 (GFPT2), the rate-limiting enzyme in HBP, is expressed on protein level in a subset of LMS and the expression of this enzyme is frequently retained in patient-matched primary and metastatic tumors. In a new independent cohort of 327 patients, we showed that GFPT2 is associated with poor outcome of uterine LMS but not extra-uterine LMS. Based on the analysis of a small group of patients studied by F-FDG-PET imaging, we propose that strong expression of GFPT2 in primary LMS may be associated with high metabolic activity. Our data suggest that HBP is a potential new therapeutic target in one of the subtypes of LMS.
肿瘤细胞的代谢重编程以及葡萄糖摄取增加是癌症的标志之一。为了确定平滑肌肉瘤（LMS）中激活的代谢途径，我们分析了多个数据集中不同亚型LMS的转录组谱。LMS亚型2中的原发性、复发性和转移性肿瘤显示出参与己糖胺生物合成途径（HBP）的基因一致富集。我们证明，HBP中的限速酶谷氨酰胺-果糖-6-磷酸转氨酶2（GFPT2）在一部分LMS中呈蛋白水平表达，并且该酶的表达在患者匹配的原发性和转移性肿瘤中经常保留。在一个由327名患者组成的新的独立队列中，我们表明GFPT2与子宫LMS的不良预后相关，但与子宫外LMS无关。基于对一小部分接受F-FDG-PET成像研究的患者的分析，我们提出原发性LMS中GFPT2的强表达可能与高代谢活性相关。我们的数据表明，HBP是LMS一种亚型中潜在的新治疗靶点。
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