PTPRO predicts patient prognosis and correlates with immune infiltrates in human clear cell renal cell carcinoma

Abstract

Background: The tumor-suppressive role of protein tyrosine phosphatase receptor type O (PTPRO) has been described in a variety of human cancers; however, the clinical significance of PTPRO in human clear cell renal cell carcinoma (ccRCC) remains unclear.Methods: PTPRO expression in renal cell carcinoma (RCC) was analyzed via the Oncomine database, Gene Expression Omnibus (GEO) datasets, and The Cancer Genome Atlas (TCGA) datasets. The Kaplan-Meier curves and Cox proportional hazards model were used to evaluate the relationship of PTPRO with overall survival in ccRCC. Gene ontology (GO) analysis and gene set enrichment analysis (GSEA) were performed to explore the signaling pathways in which PTPRO may be involved. The correlation between PTPRO and immune infiltrates in ccRCC was investigated via Tumor Immune Estimation Resource (TIMER) database. The association between PTPRO mRNA expression and its methylation in RCC was analyzed using the Cancer Cell Line Encyclopedia (CCLE) dataset, GEO dataset, and cBioPortal database.The impact of PTPRO methylation on overall survival was estimated by the MethSurv database.Results: We showed that the expression of PTPRO was significantly lower in human RCC. Moreover, the lower expression of PTPRO was associated with worse overall survival in ccRCC, particularly in the advanced stage patients. Multivariate Cox regression analysis revealed the expression of PTPRO as an independent prognostic predictor for overall survival of ccRCC. Of note, PTPRO was found to be associated with the activation of immune signaling and immune cell infiltration. Furthermore, methylation of PTPRO was prevalently observed in ccRCC, and methylation of PTPRO predicted the poor outcome of ccRCC.Conclusions: Our findings suggested that PTPRO at both RNA and DNA methylation levels had the potential as a prognostic biomarker for predicting prognosis, and PTPRO expression was closely associated with immune infiltration in ccRCC patients.

Tumor-Derived Exosomal Protein Tyrosine Phosphatase Receptor Type O Polarizes Macrophage to Suppress Breast Tumor Cell Invasion and Migration

“…In addition, the deletion of PTPRO promotes PD-L1 secretion in both monocytes and macrophages through JAK2/STAT1 and JAK2/STAT3/c-MYC pathways ( Zhang W. et al, 2020 ). Together with the finding that PTPRO expression is correlated with the activation of immune response in human clear cell renal cell carcinoma ( Gan and Zhang, 2020 ), the potential role of PTPRO in immune regulation has been noticed. In line with these studies, we found that PTPRO is closely correlated with TAMs.…”

PTPRO activates TLR4/NF-κB signaling to intensify lipopolysaccharide-induced pneumonia cell injury

“…5 PTPRO with the conserved intracellular PTP domain catalyzes dephosphorylation of tyrosine peptides in target genes, thus participating in biological processes, such as apoptosis, differentiation, and proliferation. 6 PTPRO was also found to be associated with immune infiltration in distinct cancers, 7,8 and functioned as a tumor suppressor 9 through polarization of macrophages into M1-like tumorassociated macrophages. 10 Moreover, PTPRO also plays a role in inflammation-associated tissue damage.…”

Tyrosine Phosphatase PTPRO Deficiency in ERBB2-Positive Breast Cancer Contributes to Poor Prognosis and Lapatinib Resistance

“…Protein tyrosine phosphatase receptor-type O (PTPRO), a member of the R3 subfamily of receptor protein tyrosine phosphatases (PTPs), has been found to correlate negatively with clinical aggressiveness in different malignancies (Motiwala et al, 2003;Motiwala et al, 2004;You et al, 2012;Hou et al, 2013;Huang et al, 2013;Dong et al, 2017a;Gan and Zhang, 2020). We and others have demonstrated that PTPRO is capable of dephosphorylating RTKs such as ERBB2 and EPH receptors (Shintani et al, 2006;Dong et al, 2017a) and repressing tumor growth (Motiwala et al, 2003;Motiwala et al, 2004;Dong et al, 2017a).…”