PTPRO is a therapeutic target and correlated with immune infiltrates in pancreatic cancer

Abstract

As a member of protein tyrosine phosphatases (PTPs), the protein tyrosine phosphatase receptor type O (PTPRO) has attracted increasing attention for its important roles in cell signaling. Currently, the roles of PTPRO in human cancers remain elusive. Herein, we performed bioinformatic analyses and revealed the potential oncogenic role of PTPRO in specific cancer types. Further in vitro experiments indicated that inhibition of PTPRO suppresses the proliferative abilities of tumor cells in pancreatic cancer, blood cancer, and breast cancer. Moreover, small molecular PTPRO inhibitor could induce cell apoptosis and affect the cell cycle in pancreatic cancer. In addition, PTPRO expression promoted the infiltration of CD8+ T, macrophages, dendritic cells, and neutrophils, in pancreatic cancers. Our findings suggested PTPRO may serve as a potential drug target for pancreatic cancer.

Keywords: PTPRO; biomarker; pancreatic cancer; prognosis; tumor-infiltrating.

Figure 1

Expression of PTPRO in various forms of human cancers. (A) Upregulation or downregulation of PTPRO in data sets of various cancers, relative to normal tissues based on the Oncomine database. (B) Expression of PTPRO in various types of human cancers from TCGA database as assessed via GEPIA (*P < 0.01).

Figure 2

Representative Kaplan-Meier survival curves showing the high versus low PTPRO expression in various forms of cancer based on the PrognoScan databases.

Figure 3

Kaplan-Meier survival curves showing the high versus low PTPRO expression in various cancer types based on the Kaplan-Meier plotter databases.

Figure 4

(A) The anti-proliferation activities of PTPRO inhibitor GP03 at 50μM against three cancer cell lines. (B) Effects of PTPRO knock-down on proliferation of pancreatic cancer cells. (C) Cell counts using the Celigo system (×100 magnification).

Figure 5

(A-C) Apoptosis induction of pancreatic cancer cells by DMSO and PTPRO inhibitor GP03 at 100 μM. (D-F) Cell cycle distribution of pancreatic cancer cells treated with DMSO and PTPRO inhibitor GP03 at 100 μM.

Figure 6

Gene set enrichment analysis in pancreatic cancer (PAAD) based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. PAAD samples were correlated positively with gene signatures that are linked to cytokine-cytokine receptor interaction, natural killer cell mediated cytotoxicity, and Jak-STAT signaling pathway.

Figure 7

PTPRO expression versus immune infiltration level in PAAD (pancreatic adenocarcinoma).