Research Paper|Volume 13, Issue 17|pp 21294—21308

PPM1D is a potential prognostic biomarker and correlates with immune cell infiltration in hepatocellular carcinoma

Zhangtao Yu^1,^2,³, Yinghui Song^1,^2,^3,⁴, Mengting Cai⁵, Bo Jiang^1,^2,³, Zhihua Zhang^1,^2,³, Le Wang^1,^2,³, Yu Jiang^1,^2,³, Lianhong Zou⁶, Xiehong Liu⁶, Nanhui Yu⁶, Xianhai Mao^1,^2,³, Chuang Peng^1,^2,³, Sulai Liu^1,^2,^3,⁴

¹Department of Hepatobiliary Surgery, Hunan Research Center of Biliary Disease, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha 410005, Hunan Province, China
²Clinical Medical Technology Research Center of Hunan Provincial for Biliary Disease Prevention and Treatment, Changsha 410005, Hunan Province, China
³Biliary Disease Research Laboratory of Hunan Provincial People’s Hospital, Key Laboratory of Hunan Normal University, Changsha 410005, Hunan Province, China
⁴Central Laboratory of Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha 410005, Hunan Province, China
⁵Department of Nuclear Medicine, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha 410005, Hunan Province, China
⁶Hunan Provincial Institute of Emergency Medicine, The First Affiliated Hospital of Hunan Normal University, Hunan Provincial People’s Hospital, Changsha 410005, Hunan Province, China

* Equal contribution

Received: November 5, 2020Accepted: August 10, 2021Published: September 1, 2021

https://doi.org/10.18632/aging.203459

Copyright: © 2021 Yu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: Protein phosphatase magnesium-dependent 1 delta (PPM1D), also referred to as wild-type p53-induced phosphatase 1 (Wip1) or protein phosphatase 2C delta (PP2Cδ), is an oncogenic nuclear serine/threonine phosphatase belonging to the PP2C family. However, the knowledge regarding PPM1D mRNA expression, tumor immunity, and the prognosis in hepatocellular carcinoma (HCC) is scanty.

Methods: We analyzed PPM1D, including its expression in both the normal and tumor tissue using the Sangerbox database and Tumor Immune Estimation Resource (TIMER). We evaluated its correlation with prognosis in different tumor types by the Kaplan-Meier plotter and Gene Expression Profiling Interactive Analysis (GEPIA). The correlations between PPM1D and the cancer immune infiltrates were determined using TIMER. The correlations between PPM1D expression and gene marker sets of the immune infiltrates were established by both the TIMER and GEPIA. Immunohistochemistry was performed to detect the expression of Wip1 protein encoded by PPM1D in HCC, and the relationship between Wip1 expression and the prognosis of HCC were analyzed.

Results: We found out that PPM1D mRNA expression was significantly higher in several human cancers, including HCC, than in the corresponding normal human tissues. The PPM1D mRNA high expression in HCC was significantly correlated with poor prognosis. The expression was associated with progression-free survival (PFS) in multiple HCC patients’ cohorts (PFS HR = 1.5, P = 0.0066). This was especially in early stage (stage 1) and AJCC_T 1 of HCC. Besides, PPM1D mRNA expression indicated a positive correlation with tumor-infiltrating Monocytes, tumor-associated macrophages (TAMs), M1 Macrophage, M2 Macrophage, dendritic cells (DCs), T-helper (Th) and Treg. Wip1 was higher in HCC than paracancerous tissue. High expression of Wip1 was associated with poor prognosis of HCC.

Conclusion: Our findings suggested that PPM1D mRNA is critical in activating tumor immunity. Besides, they implied that PPM1D could be a potential prognostic biomarker for cancer progression. Moreover, it correlated with tumor immune cell infiltration in HCC.