Protein tyrosine phosphatase nonreceptor 2: A New biomarker for digestive tract cancers

Abstract

In this editorial, the roles of protein tyrosine phosphatase nonreceptor 2 (PTPN2) in oncogenic transformation and tumor behavior and its potential as a therapeutic target in the context of gastrointestinal (GI) cancers are presented with respect to the article by Li et al published in ninth issue of the World Journal of Gastrointestinal Oncology. PTPN2 is a member of the protein tyrosine phosphatase family of signaling proteins that play crucial roles in the regulation of inflammation and immunity. Accordingly, early findings highlighted the contribution of PTPN2 to the pathogenesis of inflammatory and autoimmune disorders related to its dysfunction. On the other hand, recent studies have indicated that PTPN2 has many different roles in different cancer types, which is associated with the complexity of its regulatory network. PTPN2 dephosphorylates and inactivates EGFR, SRC family kinases, JAK1 and JAK3, and STAT1, STAT3, and STAT5 in cell type- and context-dependent manners, which indicates that PTPN2 can perform either prooncogenic or anti-oncogenic functions depending on the tumor subtype. While PTPN2 has been suggested as a potential therapeutic target in cancer treatment, to the best of ourknowledge, no clear treatment protocol has referred to PTPN2. Although there are only few studies that investigated PTPN2 expression in the GI system cancers, which is a potential limitation, the association of this protein with tumor behavior and the influence of PTPN2 on many therapy-related signaling pathways emphasize that PTPN2 could serve as a new molecular biomarker to predict tumor behavior and as a target for therapeutic intervention against GI cancers. In conclusion, more studies should be performed to better understand the prognostic and therapeutic potential of PTPN2 in GI tumors, especially in tumors resistant to therapy.

Keywords: Protein tyrosine phosphatase nonreceptor 2; Digestive tract cancers; Gastrointestinal cancer; Biomarker

Core Tip: Protein tyrosine phosphatase nonreceptor 2 (PTPN2) is a member of the protein tyrosine phosphatase family of signaling proteins. Numerous studies have examined the roles of this molecule in antitumor immunity and therapy because of its significant effects on a wide range of events, including the production and distribution of immune cells and numerous pathways that are important to the behavior and treatment of cancers. The role of PTPN2 in gastrointestinal (GI) cancers has been investigated in a limited number of studies, indicating that PTPN2 has heterogeneous effects on different tumors and even on the same type of GI cancer. Currently, this situation limits the recommendation of PTPN2 as a potential biomarker for predicting cancer prognosis and the efficacy of immunotherapy necessitates further studies in GI tumors.