Retrospective Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jul 15, 2021; 13(7): 716-731
Published online Jul 15, 2021. doi: 10.4251/wjgo.v13.i7.716
High expression of protein phosphatase 2 regulatory subunit B'' alpha predicts poor outcome in hepatocellular carcinoma patients after liver transplantation
Jia-Jia He, Lei Shang, Qun-Wei Yu, Ning Jiao, Shuang Qiu, Wei-Xiong Zhu, Dong-Feng Wu, Yun-Er Tian, Qing Zhang
Jia-Jia He, Qing Zhang, Clinical College of General Hospital of Chinese People's Armed Police Force, Anhui Medical University, Hefei 230032, Anhui, China
Jia-Jia He, Ning Jiao, Shuang Qiu, Wei-Xiong Zhu, Dong-Feng Wu, Yun-Er Tian, Qing Zhang, Department of Organ Transplantation, The Third Medical Center of Chinese PLA General Hospital, Beijing 100039, China
Lei Shang, Department of Health Statistics, Fourth Military Medical University, Xi'an 710032, Shanxi Province, China
Qun-Wei Yu, Department of Ophthalmology, The Third Medical Center of Chinese PLA General Hospital, Beijing 100039, China
Author contributions: He JJ, Shang L and Yu WQ contributed equally to this study; He JJ contributed to the design of the research plan, the implementation of the experiment, and the writing of the manuscript; Shang L performed the data analyses; Yu WQ performed the data collection; Jiao N and Qiu S performed the data collection and sorting; Zhu XW, Wu FD, and Tian EY reviewed the intellectual content of the article; and Zhang Q proposed research ideas and revised the final version.
Supported by National Natural Science Foundation of China, No. 81372595.
Institutional review board statement: This study was performed in compliance with the principles of the Declaration of Helsinki. The protocol was approved by the Ethics Committee of the Third Medical Center of Chinese PLA General Hospital.
Conflict-of-interest statement: The authors have no any conflicts of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Qing Zhang, PhD, Department of Organ Transplantation, Third Medical Center of Chinese PLA General Hospital, Anhui Medical University, No. 69 Yongding Road, Haidian District, Beijing 100039, China. zqy6920@sina.com
Received: March 21, 2021
Peer-review started: March 21, 2021
First decision: April 30, 2021
Revised: June 6, 2021
Accepted: June 23, 2021
Article in press: June 23, 2021
Published online: July 15, 2021
ARTICLE HIGHLIGHTS
Research background

Hepatocellular carcinoma (HCC) is one of the most common and deadly malignant tumors worldwide, and its incidence is increasing year by year. Liver transplantation (LT) is currently recognized as one of the effective methods for the treatment of HCC, but tumor recurrence and metastasis after LT restricts the long-term prognosis of patients. Therefore, it is necessary to find molecular indicators that can effectively predict the prognosis. The protein phosphatase 2 regulatory subunit B''α (PPP2R3A) gene has been found to be involved in the occurrence and development of tumors such as kidney cancer and prostate cancer. At present, it is not clear whether PPP2R3A is associated with the prognosis of HCC patients or whether it can be used as a prognostic indicator for HCC patients.

Research motivation

Effectively predicting the prognosis of LT is of great value for patients with liver cancer. PPP2R3A may be related to the occurrence and development of HCC. Our study aim is to explore the prognostic value of PPP2R3A for HCC patients after LT.

Research objectives

The main aim of the current study is to analyze the relationship between PPP2R3A and the clinicopathological characteristics of liver cancer and evaluate the prognostic value of PPP2R3A for HCC patients after LT.

Research methods

The authors used immunohistochemical methods to observe the expression of PPP2R3A in liver cancer tissues. At the same time, we collected clinical data of patients and analyzed the relationship between PPP2R3A and liver cancer by χ2 test, then performed Cox regression analysis to investigate the prognostic value of PPP2R3A for HCC patients after LT.

Research results

In immunohistochemical experiments, we detected that the expression of PPP2R3A gene in liver cancer tissues was higher than that in adjacent tissues (P ≤ 0.001), and it was mainly located in the cytoplasm of cells. χ2 test indicated that the high expression of PPP2R3A was positively correlated with AFP, TNM-t staging, and envelope invasion. In multivariate logistic regression analysis and univariate Cox proportional hazards regression analysis, PPP2R3A could be used as an independent risk factor for predicting poor prognosis of HCC patients. In addition, it was also revealed that high PPP2R3A expression combined with AFP ≥ 400 ng/mL are linked to patients with poor overall survival and recurrence-free survival rates. The 1, 2, and 3 years survival rate of patients with low PPP2R3A expression and AFP < 400 ng/mL was 98%, 80%, and 69%, respectively, while patients who met Hangzhou criteria had a post-transplant 1, 2, and 3 years overall survival rate of 89%, 66%, and 55%, respectively.

Research conclusions

PPP2R3A may be involved in the occurrence and development of liver cancer. The high expression of PPP2R3A may be a potential marker for predicting the poor prognosis and recurrence of LT for HCC patients. The combination of PPP2R3A and AFP can more accurately predict the prognosis of HCC patients after LT, supplementing and expanding the efficacy of the Hangzhou criteria.

Research perspectives

This study is the first to explore the prognostic value of PPP2R3A gene in HCC patients after LT, but the sample of the current study was relatively limited. We expect large prospective randomized controlled trials to verify further our results. In addition, a prospective validation study should be performed to confirm further the prognostic value of PPP2R3A for HCC patients after LT.