Abstract
Recent studies have revealed an oncogenic role of DJ-1 through its ability to transform normal cells, prevent oxidative damage, and inhibit apoptosis. However, its role in esophageal squamous cell carcinoma (ESCC) is unknown. In this study, by immunohistochemistry, we analyzed the expression of DJ-1 in 81 ESCC tumors, 31 paired nonneoplastic esophageal epithelia, and 19 paired ESCC lymph node metastases. We found that cytoplasmic DJ-1 expression was significantly higher in ESCC and ESCC lymph node metastases than in nonneoplastic esophageal epithelium. ESCC specimens with high distant metastatic potential also had a significantly higher level of nuclear DJ-1 expression (P = 0.018). By Kaplan-Meier analysis, we found that a high level of nuclear DJ-1 was significantly associated with poorer patient survival in our cohort (P = 0.028). To investigate whether DJ-1 promotes ESCC progression through phosphatidylinositol 3-kinase pathway and modulation of apoptosis, we performed immunohistochemistry of pAkt and Daxx. We found that DJ-1 expression was significantly associated with pAkt, whereas nuclear DJ-1 expression was significantly correlated with nuclear expression of Daxx. These results suggest that phosphatidylinositol 3-kinase pathway and Daxx-regulated apoptosis might be important in DJ-1-mediated ESCC progression. By using multivariate Cox regression, we further showed that T(4) stage (P = 0.003) and DJ-1 (P = 0.034) are independent predictors of patient survival. In conclusion, our results suggest that DJ-1 plays a very important role in transformation and progression of ESCC and may be used as a prognostic marker in ESCC.
Highlights
Esophageal squamous cell carcinoma (ESCC) is common among Asian populations
These results suggest that phosphatidylinositol 3-kinase pathway and Daxx-regulated apoptosis might be important in DJ-1-mediated ESCC progression
We observed an increase of nuclear DJ-1 expression in ESCC primary tumors compared with nonneoplastic esophageal epithelium specimens, but the difference did not reach statistical significant level (P = 0.059)
Summary
Esophageal squamous cell carcinoma (ESCC) is common among Asian populations. Despite recent advances in the detection of premalignant lesions and the development of combination therapies, its incidence is increasing and its outcome remains poor [1]. As DJ-1 has been shown to promote cell survival through the phosphatidylinositol 3-kinase (PI3K) pathway by modulating PTEN and Akt activity [13, 17] and apoptotic response through Daxx [6], we further investigated the association between DJ-1 and pAkt or Daxx in the ESCC tumor specimens. A combined score of cytoplasmic and nuclear staining was given for pAkt and DJ-1 to investigate the overall expression of these two markers on ESCC progression.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
