Department of Pathology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Cancer Sci. 2012 Jul;103(7):1363-9. doi: 10.1111/j.1349-7006.2012.02298.x. Epub 2012 Jun 4.
The object of the present study was to identify markers for predicting urinary bladder cancer progression by comparative proteome analysis of bladder cancers and paired normal mucosas. We found that DDX39 was overexpressed in four of six bladder cancers examined compared with respective control tissues. Immunohistochemical analysis using 303 bladder cancer specimens revealed that DDX39 was inversely correlated to pT stage and histological grade progression. The incidence of DDX39(high) tumors (positive cells ≥50%) was 68.6%, 43.5%, 20.0%, and 5.3% in pTa, pT1, pTis, and ≥pT2 tumors, respectively, and 65.2%, 60.7%, and 19.6% in G1, G2, and G3 tumors, respectively. The incidence of DDX39(high) tumors was significantly lower in pT1 and ≥pT2 compared to pTa tumors, and also significantly lower in G3 compared to G1 and G2 tumors. Follow-up analysis (n = 105) revealed that DDX39(low) tumors (positive cells <50%) were associated with disease progression (hazard ratio 7.485; P = 0.0083). Furthermore, DDX39-knockdown bladder cancer cells increased their invasion ability compared to negative control cells. These results suggest that DDX39 is a suppressor of invasion and loss of its function predicts disease progression in bladder cancers.
本研究旨在通过比较膀胱癌和配对正常黏膜的蛋白质组分析，鉴定预测膀胱癌进展的标志物。我们发现，与相应的对照组织相比，在检查的 6 例膀胱癌中的 4 例中过表达了 DDX39。使用 303 例膀胱癌标本进行的免疫组织化学分析表明，DDX39 与 pT 分期和组织学分级进展呈负相关。DDX39（高）肿瘤（阳性细胞≥50%）的发生率分别为 pTa、pT1、pTis 和≥pT2 肿瘤中的 68.6%、43.5%、20.0%和 5.3%，G1、G2 和 G3 肿瘤中的 65.2%、60.7%和 19.6%。与 pTa 肿瘤相比，pT1 和≥pT2 肿瘤中 DDX39（高）肿瘤的发生率明显降低，与 G1 和 G2 肿瘤相比，G3 肿瘤中 DDX39（高）肿瘤的发生率也明显降低。随访分析（n=105）显示，DDX39（低）肿瘤（阳性细胞<50%）与疾病进展相关（危险比 7.485；P=0.0083）。此外，与阴性对照细胞相比，DDX39 敲低的膀胱癌细胞增加了它们的侵袭能力。这些结果表明，DDX39 是侵袭的抑制剂，其功能的丧失预示着膀胱癌的疾病进展。
