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Elevated protein tyrosine phosphatase kappa expression is associated with disease progression and poor prognosis of pancreatic cancer
Background
Protein tyrosine phosphatase kappa (PTPRK) is a phosphatase which is recognised as a tumour suppressor. PTPRK can promote the internalization of ZNRF3 by dephosphorylating CD133. It is a negative regulator of the invasion and adhesion of breast cancer cells, what is more, it is also enhance the activation of STAT3 in lung cancer. Pancreatic exocrine cancer is an extremely aggressive tumour with a mortality being nearly equal to its incidence. The aim of present study is to assess the involvement of PTPRK in the disease progression of pancreatic cancer.
Methods
PTPRK transcripts were determined in pancreatic cancers (n=201) and adjacent non-tumour pancreatic tissues (n=201) using real time PCR. The pancreatic tissue samples were collected immediately after surgery at Peking University Cancer Hospital. All procedures used are approved by the Peking University Cancer Hospital Research Ethics Committee. The implication of PTPRK in disease progression and prognosis was analysed which was also further supported by analyses of RNAseq data of pancreatic cancer (The Cancer Genome Atlas, TCGA_PAAD) and a gene array data (GSE15471 and GSE71729). Further bioinformatic analysis has been done to determine which pathway is regulated by PTPRK.
Results
Both the public dataset GSE15471 and the Beijing clinical cohort shows increased PTPRK expression in the tumours compared with adjacent normal tissue. PTPRK expression in tumours of the earliest stage (T1) is lower than more invasive tumours (T2, T3 and T4). However, PTPRK tends to be lower in primary tumours that presented lymph node metastases. There is no significant change of PTPRK expression in the primary tumours that developed distant metastases. Moreover, PTPRK is down regulated in distant metastatic tumours from pancreatic cancer (GSE71729). Compared with lesions in the tail of pancreas, the PTPRK has also been found has a higher expression level in pancreatic head and body. Pancreatic cancer patients with a higher PTPRK level had poor overall and relapse free survival compared with patients with tumours of low PTPRK expression. In the TCGA PAAD cohort, PTPRK is positively correlated with some RTKs family gene, including EGFR, KDR, FGF and PDGF. However, neither protein level of EGFR nor phosphorylation of EGFR (Y1068 and Y1173) presented obvious difference according to PTPRK transcripts in the corresponding tumours.
Conclusions
The PTPRK is involved in pancreatic cancer progression, it is associated with a poor prognosis. Exact role played by PTPRK in pancreatic cancer and its predictive and therapeutic potential are yet to be fully investigated using both in vitro and in vivo models.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosures
All authors have declared no conflicts of interest.
