The expression patterns and the diagnostic/prognostic roles of PTPN family members in digestive tract cancers

Abstract

Background: Non-receptor protein tyrosine phosphatases (PTPNs) are a set of enzymes involved in the tyrosyl phosphorylation. The present study intended to clarify the associations between the expression patterns of PTPN family members, and diagnosis as well as the prognosis of digestive tract cancers. Methods: Oncomine and Ualcan were used to analyze PTPN expressions. Data from The Cancer Genome Atlas (TCGA) were downloaded through UCSC Xena for validation and to explore the relationship of the PTPN expression with diagnosis, clinicopathological parameters and survival of digestive tract cancers. Gene ontology enrichment analysis was conducted using the DAVID database. The gene-gene interaction network was performed by GeneMANIA and the protein-protein interaction (PPI) network was built using STRING portal coupled with Cytoscape. The expression of differentially expressed PTPNs in cancer cell lines were explored using CCLE. Moreover, by histological verification, the expression of four PTPNs in digestive tract cancers were further analyzed. Results: Most PTPN family members were associated with digestive tract cancers according to Oncomine, Ualcan and TCGA data. Several PTPN members were differentially expressed in digestive tract cancers. For esophageal carcinoma (ESCA), PTPN1 and PTPN12 levels were correlated with incidence; PTPN20 was associated with poor prognosis. For stomach adenocarcinoma (STAD), PTPN2 and PTPN12 levels were correlated with incidence; PTPN3, PTPN5, PTPN7, PTPN11, PTPN13, PTPN14, PTPN18 and PTPN23 were correlated with pathological grade; PTPN20 expression was related with both TNM stage and N stage; PTPN22 was associated with T stage and pathological grade; decreased expression of PTPN5 and PTPN13 implied worse overall survival of STAD, while elevated PTPN6 expression indicated better prognosis. For colorectal cancer (CRC), PTPN2, PTPN21 and PTPN22 levels were correlated with incidence; expression of PTPN5, PTPN12, and PTPN14 was correlated with TNM stage and N stage; high PTPN5 or PTPN7 expression was associated with increased hazards of death. CCLE analyses showed that in esophagus cancer cell lines, PTPN1, PTPN4 and PTPN12 were highly expressed; in gastric cancer cell lines, PTPN2 and PTPN12 were highly expressed; in colorectal cancer cell lines, PTPN12 was highly expressed while PTPN22 was downregulated. Results of histological verification experiment showed differential expressions of PTPN22 in CRC, and PTPN12 in GC and CRC. Conclusions: Members of PTPN family were differentially expressed in digestive tract cancers. Correlations were found between PTPN genes and clinicopathological parameters of patients. Expression of PTPN12 was upregulated in both STAD and CRC, and thus could be used as a diagnostic biomarker. Differential expression of PTPN12 in GC and CRC, and PTPN22 in CRC were presented in our histological verification experiment.