Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong, China.
Cancer Biol Ther. 2009 Aug;8(16):1534-9. doi: 10.4161/cbt.8.16.8963. Epub 2009 Aug 8.
The altered expression of human DACH1, a Drosophila Dachshund homolog, has been associated with tumor progression and metastasis. DACH1 inhibits breast cancer cellular proliferation via cyclin D1. Endometrial cancer is the third most common cancer in women and broad screening for DACH1 expression will further our understanding of this disease. Herein, we screened 126 hysterectomy specimens for DACH1 expression and evaluated the correlation between DACH1 levels and several clinical parameters. Decreased DACH1 expression was significantly correlated with FIGO surgical stages (Stage I-II vs. stage III-IV, p = 0.017), peritoneal cytology (p = 0.044), lymph node positivity (p = 0.035) and histological type (p = 0.007), but not histological grade, depth of myometrial and patient age. Immunostaining was also conducted to examine the expression of cyclin D1, estrogen receptor alpha (ERalpha) and progesterone receptor (PR) in these specimens. Multivariate analysis using the stepwise Cox proportional hazard model showed that FIGO surgical stage, histological grade, lymph node metastasis, and PR expression were correlated with poor survival. Despite the fact that univariate analysis demonstrated that DACH1 positivity is associated with increased 5-year survival in all patients (p = 0.037), decreased expression of DACH1 had no significant value as an independent prognostic factor in predicting survival in endometrial cancers. Our results suggested that loss of DACH1 expression might be involved in endometrial cancer progression.
人类 DACH1 的表达改变,一种果蝇 Dachshund 同源物,与肿瘤进展和转移有关。DACH1 通过细胞周期蛋白 D1 抑制乳腺癌细胞增殖。子宫内膜癌是女性中第三常见的癌症,广泛筛查 DACH1 的表达将进一步加深我们对这种疾病的理解。在此,我们对 126 例子宫切除术标本进行了 DACH1 表达筛选,并评估了 DACH1 水平与几个临床参数之间的相关性。DACH1 表达降低与 FIGO 手术分期(I-II 期与 III-IV 期,p=0.017)、腹膜细胞学(p=0.044)、淋巴结阳性(p=0.035)和组织学类型(p=0.007)显著相关,但与组织学分级、肌层深度和患者年龄无关。还进行了免疫组化染色,以检查这些标本中环细胞周期蛋白 D1、雌激素受体 alpha(ERalpha)和孕激素受体(PR)的表达。使用逐步 Cox 比例风险模型的多变量分析显示,FIGO 手术分期、组织学分级、淋巴结转移和 PR 表达与不良预后相关。尽管单因素分析表明 DACH1 阳性与所有患者的 5 年生存率增加相关(p=0.037),但 DACH1 表达降低作为预测子宫内膜癌生存的独立预后因素并无显著意义。我们的结果表明,DACH1 表达缺失可能参与了子宫内膜癌的进展。