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ARG1 Is a Potential Prognostic Marker in Metastatic Endometrial Cancer

  • Gynecologic Oncology: Original Article
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Abstract

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 Pten mutation as well as Pten and Mig-6 double mutations. While Pten mutation in the uterus is not sufficient for distant metastasis, mice with concurrent ablation of Mig-6 and Pten 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 Mig-6 and Pten mutations significantly increased compared to Pten mutation in the uterus. The results suggest that a high level of ARG1 is associated with poor prognosis in association with EC of mouse.

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All datasets presented in this study are included in the article. All data is real and guarantee the validity of experimental results.

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Funding

The research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number R01CA264944 (to J.W.J) and the Korean Government (MIST) under Award Number NRF-2022R1A2C1091055 (to J.Y.Y.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Author notes

  1. Dinh Nam Tran and Valery Rozen contributed equally to this study.

Authors and Affiliations

  1. Department of Obstetrics, Gynecology and Women’s Health, University of Missouri School of Medicine, 1030 Hitt Street, Columbia, MO, 65211, USA

    Dinh Nam Tran, Loan Thi Kim Nguyen, Mark I. Hunter, Tae Hoon Kim & Jae-Wook Jeong

  2. College of Human Medicine, Michigan State University, Grand Rapids, MI, 49503, USA

    Valery Rozen

  3. Department of Biomedical Laboratory Science, Yonsei University Mirae Campus, 1 Yonseidae-Gil, Wonju, Gangwon-Do, 26493, Republic of Korea

    Jin-Seok Jung & Jung-Yoon Yoo

  4. Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO, 65211, USA

    Lyndon M. Coghill

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  1. Dinh Nam Tran
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Correspondence to Jung-Yoon Yoo or Jae-Wook Jeong.

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Ethics Approval

All mice were maintained in the animal facility of the Institutional Animal Care and Use Committee of University of Missouri, and all animal experimental procedures were approved (Protocol 37148).

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43032_2024_1493_MOESM1_ESM.tif

Supplementary file1 Supplementary Figure 1. The expression of ARG1 protein in uterus of Ptend/d, Ptend/dMig-6d/d and control mice at 2 weeks of age. There are only few of ARG1 positive cells in the uterus of Ptend/d and Ptend/dMig-6d/d. ARG1 protein was not expressed in the uterus of control mice (TIF 5426 KB)

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Tran, D.N., Rozen, V., Nguyen, L.T.K. et al. ARG1 Is a Potential Prognostic Marker in Metastatic Endometrial Cancer. Reprod. Sci. (2024). https://doi.org/10.1007/s43032-024-01493-z

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