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

Jinfeng Gan; Hao Zhang

doi:10.21037/tcr-19-2808

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

Transl Cancer Res. 2020 Aug;9(8):4800-4810. doi: 10.21037/tcr-19-2808.

Authors

Jinfeng Gan¹, Hao Zhang²

Affiliations

¹ Institute of Precision Cancer Medicine and Pathology, Department of Pathology, Jinan University Medical College, Guangzhou, China.
² Research Centre of Translational Medicine, The Second Affiliated Hospital of Shantou University Medical College, Shantou, China.

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.

Keywords: Protein tyrosine phosphatase receptor type O (PTPRO); clear cell renal cell carcinoma (ccRCC); immune; methylation; prognosis.