Prognostic significance of HOXD4 protein expression in human ovarian cancers

Ovarian cancer is the most common gynecological malignancy, ranking as the fifth leading cause of cancer-related deaths among females in the United States. Homeobox D4 (HOXD4) is a transcription factor belonging to the homeobox protein family, which plays a critical role in morphogenesis during embryo development. Here we aimed to study the HOXD4 expression in ovarian serous carcinoma (OSC) and determine its clinical significance.  Real-time quantitative PCR and immunohistochemistry targeting human OSC tissues and adjacent ovarian tissues were performed to correlate the patterns of HOXD4 expression with clinical characteristics and survival outcomes. Cell lines and nude mice were used for verifying the role of HOXD4 in OSC. HOXD4 protein was predominantly expressed in OSC tissues compared with nontumorous tissues. The correlation test demonstrated a significant correlation between HOXD4 with tumor FIGO stage. Univariate and multivariate analyses found that HOXD4 expression was associated with poorer overall survival. Furthermore, high expression of HOXD4 protein was observed in OSC cell lines in vitro. Finally, the oncogenic effect of HOXD4 was confirmed by cellular and xenograft experiments. HOXD4 protein expression may be associated with a poorer prognosis in OSC. The unfavorable prognostic value of HOXD4 in malignancies and its underlying mechanism are worthy of further investigation.