Background and aims: DJ-1 and PTEN have been shown to involve
October 11, 2017
Background and aims: DJ-1 and PTEN have been shown to involve in multiple cell processes and play an important role in cancer development and progression. (P=0.001). Loss or downregulation of PTEN was found in 58.7% (67/114) and associated with advanced clinical stage (P=0.018) and high expression of DJ-1 in tumor cells (P=0.006). In univariate survival analysis, high-expression of DJ-1 or loss of PTEN was significantly associated with poor prognosis of GC patients. However, only 875320-29-9 supplier tumor depth (P=0.011) and coexistence of DJ-1 and PTEN abnormal expression (P=0.009) emerged as strong independent prognostic factors for overall survival of GC patients. Conclusions: the present study indicates that DJ-1 and PTEN may play their roles in progression of GC in a cooperating pattern. Co-existence of abnormal DJ-1 and PTEN expression is likely to serve as an independent predictive factor for prognosis of GC patients. Keywords: Gastric carcinoma, DJ-1, PTEN, 875320-29-9 supplier Metastasis, Prognosis. Introduction Gastric carcinoma (GC) is one of the most common causes of cancer-related deaths in the world, and over one-third 875320-29-9 supplier of all GCs worldwide occur Rabbit Polyclonal to Granzyme B in China 1-2. Although the combination of surgical resection and adjuvant chemo- or radiotherapy has been applied widely in China, the 5 -year survival rate of patients with GC is currently less than 20% because of the frequency of distant metastases and local recurrence. When metastasis has occurred, the patients are often unsuitable for curative surgery. Metastasis is the main cause of treatment failure and induces a poor prognosis in patients with GC 3-4. In the past two decades, various researches on GC have been preformed and tried to find the mechanism of invasion and metastasis of this tumor, but the precise molecular mechanism remains to be clarified. In fact, whether 875320-29-9 supplier or not certain molecules involved in the invasion and metastasis of GC, and consequently influenced the prognosis of GC is largely unknown. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor suppressor, also known as a key negative regulator of the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (PKB/Akt) signaling pathway 5. It has been demonstrated that PTEN affects processes such as cell cycle progression, apoptosis, migration, metabolism, transcription and translation by negatively regulating the AKT pathway and decreasing phosphorylation of AKT substrates 6. PTEN can also inhibits cell invasion and metastasis 7-8, as well as restricting cell differentiation 9. The loss or downregulation of PTEN appears to be a common event in many types of tumors. Loss of PTEN have been associated with invasive urothelial carcinoma of urinary bladder 875320-29-9 supplier 10. The PTEN gene was previously reported to be transcriptionally silenced by promoter methylation in a number of GC cases 11, and loss or reduced expression of PTEN correlated with advanced-stage GCs 12. However, the role of the loss or reduced expression of PTEN in GC’s prognosis remains unclear. DJ-1, also known as the Parkinson’s disease-associated protein 7 (PARK7), is a 189 amino acid protein with multiple functions. Accumulating evidence has shown that DJ-1 is overexpressed in many types of malignant tumors 13-14 and also correlated with tumor progression in various cancers 15-16. DJ-1 promotes cell survival by modulating PTEN 17, and high DJ-1 levels have been reported during initiation and progression in certain types of cancer 18-19. Elevated serum concentrations of DJ-1 in GC patients in high-incidence regions of gastric cancer has suggested that differing mechanisms of disease pathogenesis may be at play in high- and low-incidence regions of this tumor 20. However, the role of DJ-1 in cancer metastasis, especially its correlation to the prognosis of GC remains unclear. In the present study, we evaluate the expression of DJ-1 and PTEN in GCs and investigate their association with clinicopathological parameters to determine the role of these proteins in the prognostic significance of GC. Material and Methods Specimens of GC and Clinicopathological Findings Archival formalin-fixed, paraffin-embedded specimens from 114 primary GC patients during 2004-2007 in the first Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) were collected. The patients were 72 males and 42 females with a median age of 55 years (range 25-80). According.