Prognostic Significance of Pregnancy Zone Protein and Its Correlation with Immune Infiltrates in Hepatocellular Carcinoma

Aim: Human pregnancy zone protein (PZP) is a pregnancy -related protein which is increased dramatically during pregnancy. However, the expression of PZP and its prognostic value, association with tumor-infiltrating immune cells (TIICs) in microenvironment and potential biological process in HCC were unclear. Methods: The PZP expression, clinicopathology analysis and its influence on survival were analyzed by GEPIA and HPA. Fifty-nine HCC samples and 30 corresponding noncancerous tissues were collected and retrospectively analyzed to verify the results of bioinformatics analysis. Further, TIMER and CIBERSORT were performed to identify the significantly alerted biological process and affections of PZP expression on the immune system in patients with HCC. Finally, IHC assay of CD4(+) T cells and Treg cells was performed to confirm the results of immune infiltrates analysis by TIMER and CIBERSORT. Results: PZP expression was downregulated in HCC tissues and its low level was substantially correlated with poor prognosis in patients with HCC. TIMER analysis showed that PZP expression had a positive correlation with the levels of macrophage and neutrophil. Furthermore, CIBERSORT analysis showed that resting memory CD4 T cells were increased in high PZP expression group, while the results of Tregs were the opposite. Finally, the IHC results of CD4+ T cells and Treg cells showed that only Tregs were negatively associated with PZP expression. Conclusion: PZP was identified as a novel prognosis biomarker of HCC and might play a vital role in the regulation and recruitment of TIICs in HCC immune microenvironment.