We demonstrated reduced PTPRD expression in gastric adenocarcinoma with malignant phenotype and prognosis

The overall survival of patients with low PTPRD expression was significantly worse than that of PTPRD-high patients. These findings were similar to the previous studies in lung cancer and glioblastoma by Veeriah et al.. Taken together, these results demonstrated that PTPRD might serve as a tumor suppressor in a broad spectrum of human tumor types. Univariate and multivariate analysis demonstrated that PTPRD was an independent risk factor in the prognosis of GC patients. Thus, PTPRD may serve as a valuable prognostic biomarker for GC patients after surgery and as a potential target for gene therapy in the treatment of GC. PTPRD encodes a transmembrane protein with a cytoplasmic tyrosine phosphatase domain. Recently, a study by Veeriah et al. revealed that loss of PTPRD resulted in altered growth of astrocytes. PTPRD directly dephosphorylates the oncoprotein STAT3 and regulates the STAT3 pathway. Mutations in PTPRD abrogate the ability to regulate STAT3. Their results suggest that PTPRD may act as a tumor suppressor by regulating cell growth, and the loss of this gene plays an important role in progression, rather than the initiation of malignant gliomas. In the current study, we found that the loss of PTPRD expression was significantly correlated with a higher T stage of gastric cancer, implying that absence of PTPRD expression may promote tumor growth and invasion. Moreover, we detected lower PTPRD immunoreactivity in poorly differentiated gastric cancer tissues than in well-differentiated ones, suggesting that decreased PTPRD expression might play a role in tumor de-differentiation. Furthermore, we investigated the functional role of PTPRD in MGC803 and GES1 cell lines. Restoring PTPRD expression in GC cells significantly inhibited cell proliferation. Whereas, silencing PTPRD expression in gastric epithelial cells significantly enhanced the cell growth rate. These results indicated that PTPRD might play an import role in regulating gastric cancer cell growth. Recently, Veeriah’s research showed that human astrocytes lacking PTPRD exhibited increased growth. Our study, together with that of Veeriah et al., suggested that PTPRD might serve as a candidate tumour suppressor in a wide range of common human tumor types. However, the functional role and molecular underpinnings of PTPRD in GC have not been fully explored, requiring further investigation in future research. DNA hypermethylation in BMS-354825 promoter CpG island has been shown to be a predominant mechanism by which tumor suppressors are inactivated in cancers. In the present study, methylation analysis of PTPRD promoter CpG island in 3 primary GC samples showed one case with partial methylation. Low PTPRD expression in most GC tissues was probably due to DNA methylation of promoter CpG island. Recently, two studies showed DNA hypermethylation of PTPRD in glioblastoma and breast cancer cell lines. These researches indicated that the methylation of CpG in the PTPRD promoter was might be involved in the inactivation of PTPRD in many types of human cancers.

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