Yuen Hiu-Fung, Chan Yuen-Piu, Law Simon, Srivastava Gopesh, El-Tanani Mohamed, Mak Tak-Wah, Chan Kwok-Wah
Department of Pathology, Queen Mary Hospital, Hong Kong, People's Republic of China.
Cancer Epidemiol Biomarkers Prev. 2008 Dec;17(12):3593-602. doi: 10.1158/1055-9965.EPI-08-0214.
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.
近期研究表明，DJ-1具有致癌作用，它能够转化正常细胞、预防氧化损伤并抑制细胞凋亡。然而，其在食管鳞状细胞癌（ESCC）中的作用尚不清楚。在本研究中，我们通过免疫组织化学分析了DJ-1在81例ESCC肿瘤、31对非肿瘤性食管上皮以及19对ESCC淋巴结转移灶中的表达情况。我们发现，ESCC及ESCC淋巴结转移灶中DJ-1的细胞质表达显著高于非肿瘤性食管上皮。具有高远处转移潜能的ESCC标本中，核DJ-1表达水平也显著更高（P = 0.018）。通过Kaplan-Meier分析，我们发现高水平的核DJ-1与本队列中患者较差的生存率显著相关（P = 0.028）。为了研究DJ-1是否通过磷脂酰肌醇3-激酶途径和细胞凋亡调节促进ESCC进展，我们进行了pAkt和Daxx的免疫组织化学检测。我们发现DJ-1表达与pAkt显著相关，而核DJ-1表达与Daxx的核表达显著相关。这些结果表明，磷脂酰肌醇3-激酶途径和Daxx调节的细胞凋亡可能在DJ-1介导的ESCC进展中起重要作用。通过多变量Cox回归分析，我们进一步表明T(4)期（P = 0.003）和DJ-1（P = 0.034）是患者生存的独立预测因素。总之，我们的结果表明DJ-1在ESCC的转化和进展中起着非常重要的作用，并且可能用作ESCC的预后标志物。
