These studies demonstrate that B7-H4 directly promotes malignant transformation of ovarian cancer cell line, and provides a potential therapeutic strategy for targeting B7-H4 to inhibit progression of human ovarian cancers.
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 (ERα) 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.
The altered DEGs (ZEB1, ZEB2, TIMP2, TCF4, CYP1B1, PITX1, PITX2, ZNF154 and TSPYL5) may be involved in tumor differentiation of endometrioid endometrial adenocarcinoma and could be used as potential therapeutic targets for the disease.
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