Wenle Li1,2#, Zherui Liu3#, Wei Chen4, Xiaodong Jia5* and Chengliang Yin6*
1Department of Orthopedics, Xianyang Central Hospital, China
2Clinical Medical Research Center, Xianyang Central Hospital, China
3Peking University, Clinical Medical School, Beijing, China
4Department of Laboratory Medicine, Hospital of People`s Liberation Army Ground Force, China
5Comprehensive Liver Cancer Center, The Fifth Medical Center of PLA General Hospital, Beijing, China
6Macau University of Science and Technology, Macau, China
#These authors contributed equally to this work
Protein Z (PROZ) is a liver vitamin K-dependent glycoprotein, which has been associated with some cancer types; however, its role and mechanism in Hepatocellular Carcinoma (HCC) development and progression remain unclear. We used public datasets of cancer tissues and cell lines from the Oncomine and Human Protein Atlas to compare the expression of PROZ in various cancer types. The PROZ expression level was the highest in HCC. PROZ expression was decreased in HCC compared with normal tissues. A higher PROZ level was positively correlated with favorable overall survival, disease-free survival, progression-free survival, relapse-free survival, and disease-specific survival in patients with HCC. These results were validated in clinical HCC patient’s survival information. Moreover, the expression levels of microRNAs predicted to target PROZ were inversely correlated with overall survival in HCC patients. Notably, a higher expression level of PROZ was associated with a lower risk of progression in HCC patients at stage I or without vascular invasion. The correlations of PROZ expression with the numbers of tumor-infiltrating cells and their marker genes were further analyzed using tumor immune estimation resource and GEPIA tools. PROZ expression was negatively correlated with the numbers of tumor-infiltrating CD8+ T cells, CD4+ T cells, macrophages, and neutrophils in HCC, but was positively correlated with the level of INOS, a marker of M1 macrophages. Overall, these results indicate that PROZ is a tumor-suppressor gene, and could serve as a biomarker for early HCC progression, which may be attributed to its influence on tumor-infiltrating cells.
Li W, Liu Z, Chen W, Jia X, Yin C. PROZ is a Biomarker for Progression of Early Hepatocellular Carcinoma and Correlated with Tumor-Infiltrating Immune Cells. Clin Surg. 2022; 7: 3433..