PROZ, also known as the gene encoding vitamin K-dependent protein Z, is a gene with notable functions in the body. Protein Z is canonically considered to have anticoagulant effects through negative regulation of factor Xa [4]. It is involved in the coagulation pathway and has implications for maintaining vascular homeostasis [5].

In hepatocellular carcinoma, low PROZ expression was significantly correlated with poor prognosis. It was also closely related to the expression of p-ERK and VEGFR2, and was negatively correlated with genes related to immunotherapy efficacy and T-cell infiltration in tumor tissue, suggesting it may be a potential target to enhance the efficacy of combined immunotherapy [1]. In early hepatocellular carcinoma, PROZ expression was decreased compared to normal liver controls, and low PROZ expression was associated with poor overall survival [2]. In the context of hypercoagulability, biallelic variants in PROZ may be a cause [3]. In the UK Biobank study, loss of function in PROZ was associated with an increased risk of non-cardioembolic ischemic stroke [4]. In a multi-ethnic study of young and middle-aged adults, there was a non-linear positive association between PZ level (encoded by PROZ) and unexplained stroke [6]. Polymorphisms of PROZ were associated with recurrent spontaneous abortion in Chinese Han women [7]. In preterm birth, increased PROZ expression in amniotic fluid was associated with the occurrence of PTB, and PROZ promoted the proliferation and migration of amniotic membrane fibroblasts [8].

In conclusion, PROZ plays a crucial role in multiple biological processes and disease conditions, especially in coagulation-related disorders and some cancers. The study of PROZ in these disease areas helps to understand the underlying molecular mechanisms, providing potential directions for diagnosis, prognosis, and treatment [1-4, 7].

References:

1. Chen, Yinkui, Qiu, Xiusheng, Wu, Donghao, Xiong, Zhiyong, Wang, Tiantian. 2022. PROZ Associated with Sorafenib Sensitivity May Serve as a Potential Target to Enhance the Efficacy of Combined Immunotherapy for Hepatocellular Carcinoma. In Genes, 13, . doi:10.3390/genes13091535. https://pubmed.ncbi.nlm.nih.gov/36140703/

2. Jiang, Xiaocong, Song, Ting, Pan, Xiuhua, Lan, Yuhong, Bai, Li. 2021. PROZ May Serve as a Prognostic Biomarker for Early Hepatocellular Carcinoma. In International journal of general medicine, 14, 4209-4218. doi:10.2147/IJGM.S311959. https://pubmed.ncbi.nlm.nih.gov/34393500/

3. Pinto E Vairo, Filippo, Kroc, Sarah A, Bertsch, Nicole L, Zimmermann, Michael T, Klee, Eric W. 2020. Biallelic variants in PROZ as a cause of hypercoagulability and livedo racemosa. In Thrombosis research, 195, 187-189. doi:10.1016/j.thromres.2020.07.014. https://pubmed.ncbi.nlm.nih.gov/32721632/

4. Haj, Amelia K, Ryu, Justine, Jurgens, Sean J, Ellinor, Patrick T, Bendapudi, Pavan K. 2024. Loss of function in protein Z (PROZ) is associated with increased risk of ischemic stroke in the UK Biobank. In Journal of thrombosis and haemostasis : JTH, 23, 171-180. doi:10.1016/j.jtha.2024.09.016. https://pubmed.ncbi.nlm.nih.gov/39383998/

5. Ranjan, Gyan, Sehgal, Paras, Scaria, Vinod, Sivasubbu, Sridhar. 2024. SCAR-6 elncRNA locus epigenetically regulates PROZ and modulates coagulation and vascular function. In EMBO reports, 25, 4950-4978. doi:10.1038/s44319-024-00272-w. https://pubmed.ncbi.nlm.nih.gov/39358551/

6. Zhang, Lili, Segal, Alan Z, Leifer, Dana, Devereux, Richard B, Kizer, Jorge R. 2016. Circulating protein Z concentration, PROZ variants, and unexplained cerebral infarction in young and middle-aged adults. In Thrombosis and haemostasis, 117, 149-157. doi:10.1160/TH16-04-0277. https://pubmed.ncbi.nlm.nih.gov/27683756/

7. Xu, Zuying, Zhang, Ying, Liu, Wei, Cao, Yunxia, Xiang, Huifen. 2018. Polymorphisms of F2, PROC, PROZ, and F13A1 Genes are Associated With Recurrent Spontaneous Abortion in Chinese Han Women. In Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis, 24, 894-900. doi:10.1177/1076029617750487. https://pubmed.ncbi.nlm.nih.gov/29363996/

8. Chen, Siguo, Wang, Weizhou, Yan, Guanghong, Zhou, Linglin, You, Dingyun. 2024. Amniotic Fluid Proteomics Analysis and In Vitro Validation to Identify Potential Biomarkers of Preterm Birth. In Reproductive sciences (Thousand Oaks, Calif.), 31, 2032-2042. doi:10.1007/s43032-024-01457-3. https://pubmed.ncbi.nlm.nih.gov/38453771/