Glutathione peroxidase 1 (GPx1), the first identified selenoprotein, is a widely-expressed antioxidant enzyme. It utilizes glutathione to catalyze hydrogen peroxide, lipid peroxide, and peroxynitrite, reducing intracellular oxidative stress. GPx1 modulates the balance of reactive oxygen species, and its gene is regulated at transcriptional, post-transcriptional, and translational levels [2,4].

In acute myeloid leukemia (AML), high GPX1 expression links to poor prognosis, is associated with immunosuppression-related cell fractions and markers, and its silencing reduces AML cell viability [1]. In laryngeal squamous cell carcinoma (LSCC), high GPX1 expression correlates with lymph node metastasis, TNM stage, and poor prognosis [3]. In brain lower-grade glioma (LGG), GPX1 overexpression is linked to poor prognosis, and its interaction with chemoradiotherapy may improve the outcome; it also predicts temozolomide sensitivity [5]. In the aging lens, GPX1 knockout causes accelerated cataract development, indicating its importance for lens transparency [6]. In macrophages from active Crohn's disease patients, GPX1 deficiency increases susceptibility to ferroptosis [7]. In kidney cancer, GPX1 is highly expressed, positively correlated with metastasis and poor survival, and may serve as a diagnostic and prognostic biomarker [8].

In conclusion, GPX1 is crucial for maintaining redox balance in various tissues. Gene knockout models, such as in the lens and macrophages, have revealed its role in preventing age-related cataracts and in the pathophysiology of Crohn's disease respectively. In cancer, high GPX1 expression often predicts poor prognosis, highlighting its potential as a biomarker and therapeutic target in multiple malignancies.

References:

1. Zhang, Jian, Peng, Yuhui, He, Yan, Guo, Penxiang, Zhang, Qifang. 2021. GPX1-associated prognostic signature predicts poor survival in patients with acute myeloid leukemia and involves in immunosuppression. In Biochimica et biophysica acta. Molecular basis of disease, 1868, 166268. doi:10.1016/j.bbadis.2021.166268. https://pubmed.ncbi.nlm.nih.gov/34536536/

2. Zhao, Yangjing, Wang, Hui, Zhou, Jingdong, Shao, Qixiang. 2022. Glutathione Peroxidase GPX1 and Its Dichotomous Roles in Cancer. In Cancers, 14, . doi:10.3390/cancers14102560. https://pubmed.ncbi.nlm.nih.gov/35626163/

3. Zhang, Qicheng, Xu, Hongli, You, Yiwen, Zhang, Jie, Chen, Renjie. 2017. High Gpx1 expression predicts poor survival in laryngeal squamous cell carcinoma. In Auris, nasus, larynx, 45, 13-19. doi:10.1016/j.anl.2017.05.012. https://pubmed.ncbi.nlm.nih.gov/28641905/

4. Handy, Diane E, Loscalzo, Joseph. 2022. The role of glutathione peroxidase-1 in health and disease. In Free radical biology & medicine, 188, 146-161. doi:10.1016/j.freeradbiomed.2022.06.004. https://pubmed.ncbi.nlm.nih.gov/35691509/

5. Chen, Xueqin, Fu, Guotao, Li, Linglan, Ke, Zunhua, Zhang, Rongqiang. 2022. Selenoprotein GPX1 is a prognostic and chemotherapy-related biomarker for brain lower grade glioma. In Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS), 74, 127082. doi:10.1016/j.jtemb.2022.127082. https://pubmed.ncbi.nlm.nih.gov/36155420/

6. Varadaraj, Kulandaiappan, Gao, Junyuan, Mathias, Richard T, Kumari, S Sindhu. 2022. GPX1 knockout, not catalase knockout, causes accelerated abnormal optical aberrations and cataract in the aging lens. In Molecular vision, 28, 11-20. doi:. https://pubmed.ncbi.nlm.nih.gov/35400989/

7. Sousa, James A, Callejas, Blanca E, Wang, Arthur, Raman, Maitreyi, McKay, Derek M. 2024. GPx1 deficiency confers increased susceptibility to ferroptosis in macrophages from individuals with active Crohn's disease. In Cell death & disease, 15, 903. doi:10.1038/s41419-024-07289-y. https://pubmed.ncbi.nlm.nih.gov/39695083/

8. Cheng, Yongbiao, Xu, Tianbo, Li, Sen, Ruan, Hailong. 2019. GPX1, a biomarker for the diagnosis and prognosis of kidney cancer, promotes the progression of kidney cancer. In Aging, 11, 12165-12176. doi:10.18632/aging.102555. https://pubmed.ncbi.nlm.nih.gov/31844035/