Tran Dinh Nam, Rozen Valery, Hunter Mark I, Kim Tae Hoon, Jeong Jae-Wook
University of Missouri School of Medicine.
Michigan State University College of Human Medicine.
Res Sq. 2023 Jul 18:rs.3.rs-2917380. doi: 10.21203/rs.3.rs-2917380/v1.
Endometrial cancer (EC) is the most common gynecologic malignancy. While the majority of patients present with early-stage and low-grade EC and have an excellent prognosis, a subset has metastatic disease at presentation, or develops distant recurrence after initial treatment of the primary. However, the lack of prognostic biomarkers for metastatic EC is a critical barrier. Arginase 1 (ARG1) regulates the last step of the urea cycle, and an increase in ARG1 has been correlated as a poor prognostic factor in a variety of cancers. In the present study, ARG1 expression was evaluated as a potential prognostic marker for metastatic EC in endometrial hyperplasia and cancer of mice with mutation as well as double mutations. While mutation in the uterus is not sufficient for distant metastasis, mice with concurrent ablation of and develop distant metastasis. Our immunostaining and RT-qPCR analysis revealed that the expression of ARG1 in early stage of EC as well as endometrial hyperplasia from mice deficient in and mutations significantly increased compared to mutation in the uterus. The results suggest that a high level of ARG1 is associated with poor prognosis in association with EC of mouse.
子宫内膜癌(EC)是最常见的妇科恶性肿瘤。虽然大多数患者表现为早期和低级别EC,预后良好,但有一部分患者在初诊时就有转移性疾病,或在原发灶初始治疗后发生远处复发。然而,缺乏转移性EC的预后生物标志物是一个关键障碍。精氨酸酶1(ARG1)调节尿素循环的最后一步,ARG1的增加已被认为是多种癌症的不良预后因素。在本研究中,评估了ARG1表达作为具有 突变以及 双突变的小鼠子宫内膜增生和癌症中转移性EC的潜在预后标志物。虽然子宫中的 突变不足以发生远处转移,但同时缺失 和 的小鼠会发生远处转移。我们的免疫染色和RT-qPCR分析显示,与子宫中的 突变相比,缺乏 和 突变的小鼠在EC早期以及子宫内膜增生中ARG1的表达显著增加。结果表明,高水平的ARG1与小鼠EC的不良预后相关。