Abstract
Background PTPRD, encoding protein tyrosine phosphatases receptor type D, is located at chromosome 9p23–24.1, a loci frequently lost in many types of tumors. Recently, PTPRD has been proposed to function as a tumor suppressor gene. The current study aimed to investigate PTPRD expression and its prognostic significance in primary gastric adenocarcinoma.Methods and ResultsQuantitative real time reverse transcription PCR (qRT-PCR) and western blotting were used to examine PTPRD expression in paired gastric tumourous and paracancerous tissues. Compared with the matched normal gastric mucosa tissues, both the mRNA (P = 0.0138) and protein (P = 0.0093) expression of PTPRD in fresh surgical specimens were significantly reduced. Clinicopathological and prognostic roles of PTPRD in gastric adenocarcinoma were investigated using immunohistochemistry with 513 paraffin-embedded gastric adenocarcinoma tissue blocks. Statistical analysis revealed that reduced PTPRD expression was significantly associated with T stage (P = 0.004), TNM stage (P<0.001) and tumor size (P = 0.003). Furthermore, Kaplan-Meier survival analysis revealed that low expression of PTPRD significantly correlated with poor survival of gastric cancer patients (P<0.001). Cox regression analysis confirmed PTPRD expression as independent predictor of the overall survival of gastric cancer patients. The MTT assay determined the effects of PTPRD on cell proliferation of MGC803 and GES1 cell lines. Restoring PTPRD expression in MGC803 cells significantly inhibited their growth rate. Silencing PTPRD expression by siRNA treatment in GES1 significantly enhanced cell proliferation compared with mock siRNA treatment. Methylation analysis of PTPRD promoter CpG island in 3 primary GC samples showed one case with partial methylation.ConclusionsThese results indicated that PTPRD is a candidate tumour suppressor in gastric cancer. Thus, PTPRD may play an important role in gastric tumorigenesis and serve as a valuable prognostic marker of gastric adenocarcinoma.
Highlights
Gastric cancer (GC) is currently the fourth most common malignancy and the second leading cause of cancer mortality [1]
The mRNA level of PTPRD was examined by quantitative real-time reverse transcription PCR (qRT-PCR) assays in 42 paired gastric cancerous and matched adjacent normal mucosa tissues
To further investigate if the expression of PTPRD is reduced at the protein level in gastric adenocarcinoma, western blotting was performed on 23 paired gastric cancerous and noncancerous specimens
Summary
Gastric cancer (GC) is currently the fourth most common malignancy and the second leading cause of cancer mortality [1]. Tumorigenesis of GC has been considered a multifactorial and multistep process that involves the activation of oncogenes and the inactivation of tumor suppressor genes at different stages [4]. Further understanding of these alterations and the molecular mechanisms involved in gastric carcinogenesis will be critical for improved diagnosis, therapy and prognosis of GC. Statistical analysis revealed that reduced PTPRD expression was significantly associated with T stage (P50.004), TNM stage (P,0.001) and tumor size (P50.003). Kaplan-Meier survival analysis revealed that low expression of PTPRD significantly correlated with poor survival of gastric cancer patients (P,0.001). The MTT assay determined the effects of PTPRD on cell proliferation of PLOS ONE | DOI:10.1371/journal.pone.0113754 November 20, 2014
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