Li HY, Jing YM, Shen X, Tang MY, Shen HH, Li XW, Wang ZS, Su F. Protein tyrosine phosphatase non-receptor II: A possible biomarker of poor prognosis and mediator of immune evasion in hepatocellular carcinoma. World J Gastrointest Oncol 2024; 16(9): 3913-3931 [DOI: 10.4251/wjgo.v16.i9.3913]
Corresponding Author of This Article
Fang Su, Doctor, MD, PhD, Academic Research, Researcher, Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical University, No. 287 Changhuai Road, Longzihu District, Bengbu 233000, Anhui Province, China. sufang2899@163.com
Research Domain of This Article
Oncology
Article-Type of This Article
Clinical and Translational Research
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
Hui-Yuan Li, Xue Shen, Ming-Yue Tang, Hong-Hong Shen, Xin-Wei Li, Zi-Shu Wang, Fang Su, Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical University, Bengbu 233000, Anhui Province, China
Yi-Ming Jing, Department of Neurology, The First Affiliated Hospital of Bengbu Medical University, Bengbu 233000, Anhui Province, China
Author contributions: Li HY, Jing YM, Tang MY, and Su F designed and wrote the manuscript; Li HY completed the experiments; Li HY, Jing YM, Shen HH, and Li XW analyzed the data; Li HY, Jing YM, Shen X, Li XW, and Wang ZS were responsible for the literature search to improve the work and revise the manuscript. All authors reviewed the manuscript and approved its publication.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Fang Su, Doctor, MD, PhD, Academic Research, Researcher, Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical University, No. 287 Changhuai Road, Longzihu District, Bengbu 233000, Anhui Province, China. sufang2899@163.com
Received: March 28, 2024 Revised: June 3, 2024 Accepted: July 8, 2024 Published online: September 15, 2024 Processing time: 164 Days and 21.6 Hours
Abstract
BACKGROUND
The incidence of primary liver cancer is increasing year by year. In 2022 alone, more than 900000 people were diagnosed with liver cancer worldwide, with hepatocellular carcinoma (HCC) accounting for 75%-85% of cases. HCC is the most common primary liver cancer. China has the highest incidence and mortality rate of HCC in the world, and it is one of the malignant tumors that seriously threaten the health of Chinese people. The onset of liver cancer is occult, the early cases lack typical clinical symptoms, and most of the patients are already in the middle and late stage when diagnosed. Therefore, it is very important to find new markers for the early detection and diagnosis of liver cancer, improve the therapeutic effect, and improve the prognosis of patients. Protein tyrosine phosphatase non-receptor 2 (PTPN2) has been shown to be associated with colorectal cancer, triple-negative breast cancer, non-small cell lung cancer, and prostate cancer, but its biological role and function in tumors remain to be further studied.
AIM
To combine the results of relevant data obtained from The Cancer Genome Atlas (TCGA) to provide the first in-depth analysis of the biological role of PTPN2 in HCC.
METHODS
The expression of PTPN2 in HCC was first analyzed based on the TCGA database, and the findings were then verified by immunohistochemical staining, quantitative real-time polymerase chain reaction (qRT-PCR), and immunoblotting. The value of PTPN2 in predicting the survival of patients with HCC was assessed by analyzing the relationship between PTPN2 expression in HCC tissues and clinicopathological features. Finally, the potential of PTPN2 affecting immune escape of liver cancer was evaluated by tumor immune dysfunction and exclusion and immunohistochemical staining.
RESULTS
The results of immunohistochemical staining, qRT-PCR, and immunoblotting in combination with TCGA database analysis showed that PTPN2 was highly expressed and associated with a poor prognosis in HCC patients. Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that PTPN2 was associated with various pathways, including cancer-related pathways, the Notch signaling pathway, and the MAPK signaling pathway. Gene Set Enrichment Analysis showed that PTPN2 was highly expressed in various immune-related pathways, such as the epithelial mesenchymal transition process. A risk model score based on PTPN2 showed that immune escape was significantly enhanced in the high-risk group compared with the low-risk group.
CONCLUSION
This study investigated PTPN2 from multiple biological perspectives, revealing that PTPN2 can function as a biomarker of poor prognosis and mediate immune evasion in HCC.
Core Tip: Our results of immunohistochemical staining, quantitative real-time polymerase chain reaction, and immunoblotting in combination with those obtained from The Cancer Genome Atlas database showed that protein tyrosine phosphatase non-receptor 2 (PTPN2) was highly expressed in patients with hepatocellular carcinoma (HCC) and was associated with a poor prognosis. Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that PTPN2 was associated with multiple pathways, including cancer-related pathway, the Notch signaling pathway, and the MAPK signaling pathway. Analysis by constructing a risk model based on PTPN2 revealed that immune escape was significantly enhanced in the high-risk group compared with the low-risk group. In this study, PTPN2 was investigated from multiple biological perspectives, and was found to have the potential to serve as a biomarker of poor prognosis in HCC and to mediate immune escape.
