DJ‐1: A novel independent prognostic marker for survival in glottic squamous cell carcinoma

Abstract

DJ-1 is frequently overexpressed in a large variety of solid tumors, but the DJ-1 expression in laryngeal squamous cell cancer and its clinical ⁄ prognostic significance is unclear. We aimed to evaluate DJ-1 protein expression in glottic squamous cell carcinoma (GSCC) and to correlate this with clinicopathological data including patient survival. The expression of DJ-1 in GSCCs (60) and adjacent normal tissue (44) was assessed by immunohistochemistry and western blot analysis. In addition, the role of DJ-1 was investigated in tumorigenesis by transfecting DJ1-specific siRNA into laryngeal squamous cell carcinoma (LSCC) Hep-2 cells. Our data showed that positive expression of DJ-1 was found in 85% of GSCCs. In univariate survival analysis of the GSCC cohorts, a highly significant association between DJ-1 expression with shortened patient overall survival (5-year survival rate 92.9% vs 66.6%; P = 0.001; log rank test) was demonstrated. In multivariate analyses, DJ-1, tumor grading, and pT status were significant prognostic parameters for shortened patient overall survival. Furthermore, siRNA targeting DJ-1 can effectively inhibit DJ-1 expression, resulting in enhanced apoptosis and less proliferation of Hep-2 cells. We concluded that DJ-1 overexpression might be a novel independent molecular marker for poor prognosis (shortened overall survival) of patients with GSCC. (Cancer Sci 2010; 101: 1320-1325 L aryngeal carcinoma accounts for approximately 2.4% of new malignancies worldwide every year, of which over 95% are of the squamous cell carcinoma.(1,2) Glottic squamous cell carcinoma (GSCC) is the most common type of laryngeal cancer. Patients with GSCC often display considerable variability in survival.(3) It is of general importance to predict the biology of the tumor and, thus, the course of the disease in the individual patient to ensure adequate therapy and patient surveillance. Conventional prognostic and predictive markers for GSCC are nodal status, tumor grade, tumor status, and tumor type.(3) Additionally, molecular markers are being sought and established to allow for a refined classification of prognosis, especially in patient subgroups whose outcome can only insufficiently be predicted by conventional parameters. These include, among others, activation of various oncogenes (Ras, (4,5) Myc,epidermal growth factor receptor,and cyclin D1 (8) ), and tumor suppressor gene inactivation (P53 and p16).(9,10) However, accurate and reliable biomarkers that serve for prognosis have yet to be identified.DJ-1 encodes a conserved protein belonging to the ThiJ ⁄ PfpI ⁄ DJ-1 superfamily.(11) The THEMATICS (theoretical microscopic titration curves) predicted eight DJ-1 family members and three different probable functional classes.(12) The exact molecular function of DJ-1 is still unclear although increasing evidence suggests that DJ-1 plays a role in cancer cell lines to protect against stress (13)(14)(15) and affects cell survival by modulating the phosphorylation status of protein kinase B (PKB) ⁄ Akt, (16)(17)(18)...

Overexpression of DJ-1 and HSP90α, and loss of PTEN associated with invasive urothelial carcinoma of urinary bladder: Possible prognostic markers

“…This result supports previous findings that high levels of DJ-1 expression are associated with a higher pathological tumor stage in SCCs of the esophagus and glottis (14,24). These studies report that a higher expression of DJ-1 was observed in pT3-pT4 glottic SCCs compared with pTis-pT2 tumors (24) and in T4 esophageal SCCs compared with T1-T3 tumors (14). Taken together, these results indicate that a high expression of DJ-1 is associated with tumor invasiveness in carcinomas.…”

Oxidized DJ-1 Inhibits p53 by Sequestering p53 from Promoters in a DNA-Binding Affinity-Dependent Manner

“…It has been reported that DJ-1 is overexpressed in many types of cancers, especially in cancer cells with poor prognosis, and that almost half of these cancer cells possess p53 mutations (48)(49)(50)(51)(52). In this study, DJ-1 inhibited the transcriptional activities of p53 mutants more effectively than that of wild-type p53 after the cells had been exposed to H 2 O 2 (Fig.…”

Effect of DJ-1 overexpression on the proliferation, apoptosis, invasion and migration of laryngeal squamous cell carcinoma SNU-46 cells through PI3K/AKT/mTOR

“…Zhu et al used immunohistochemistry to detect tumor tissues of 7l postoperative patients with laryngeal squamous cell carcinoma and laryngeal mucosa of 9 patients with non-laryngeal who were treated between January 1995 and January 2006. After analyzing the relationship between DJ-1 protein expression and clinicopathological features, they found DJ-l protein expression levels in laryngeal squamous cell carcinoma were higher than in normal laryngeal mucosa, and survival rates may be lower for laryngeal cancer patients with higher levels of DJ-1 protein expression (23). In 2012, Zhu et al also found that the DJ-l protein overexpression in tumor tissue of supraglottic laryngeal squamous cell carcinoma was associated with lymph node metastasis.…”

“…In the present study, after flow cytometry detection with Annexin V/PI apoptosis kit, the results showed that the apoptosis rate of SNU-46-D1 was significantly lower than the rates of cell lines SNU-46 and SNU-46-CON, suggesting that overexpression of the DJ-1 gene inhibited apoptosis of laryngeal cancer cells. Previous reports showed that DJ-1 gene silencing can induce apoptosis of laryngeal cancer Hep-2 cells (23). Therefore, the DJ-1 gene may play a role in inhibiting apoptosis of laryngeal cancer cells to prolong laryngeal cell survival time and provide the conditions for the growth of laryngeal cancer cells.…”