RESUMO
BACKGROUND: Homeobox B4 (HOXB4) is correlated with poor prognosis of various cancer types. However, how HOXB4 promotes ovarian cancer (OV) progression remains unclear. METHODS: The Cancer Genome Atlas (TCGA) database indicated that a high level of HOXB4 in OV was correlated with poor prognosis. The biological functions of HOXB4 were confirmed by colony formation, migration, and invasion assays. The effect of HOXB4 on the expression of EMT cell markers was determined. The transcriptional target of HOXB4 was DHDDS, which was detected by a ChIP assay. A xenograft tumor model was generated in nude mice to detect the role of HOXB4 in tumor proliferation and metastasis. RESULTS: The results showed that HOXB4 protein levels were higher in OV tissues than in normal tissues and correlated with poor prognosis of OV. HOXB4 reduction inhibited the proliferation and invasion ability of OV cells in vitro. Conversely, these effects were enhanced by the upregulation of HOXB4 in OV cells. The binding of HOXB4 to two DNA motifs regulated DHDDS expression and contributed to the malignant progression of OV. The role of HOXB4 in contributing to tumor development in vivo was verified in mice. Further results indicated that HOXB4 induced Snail and Zeb1 expression. CONCLUSION: Overall, HOXB4 overexpression was remarkably correlated with poor prognosis of OV. Mechanistically, HOXB4 enhances the proliferation and invasion of tumor cells by activating DHDDS, thereby promoting the malignant progression of OV.
Assuntos
Alquil e Aril Transferases/genética , Carcinoma Epitelial do Ovário/patologia , Proteínas de Homeodomínio/metabolismo , Neoplasias Ovarianas/patologia , Fatores de Transcrição/metabolismo , Animais , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Xenoenxertos , Proteínas de Homeodomínio/genética , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Metástase Neoplásica , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Interferência de RNA , RNA Interferente Pequeno , Fatores de Transcrição/genética , Regulação para CimaRESUMO
BACKGROUND: Computed tomography (CT) has been extensively used in predicting suboptimal cytoreduction (SCR) in advanced ovarian cancer (OC). However, disagreements remain in literatures on the predictive value of CT findings for SCR. This meta-analysis was designed to determine the ability of eight preoperative CT findings to predict SCR in advanced OC. MATERIALS AND METHODS: A comprehensive literature search was conducted for eligible studies to identify the association between the eight preoperative CT findings and SCR in advanced OC. The predictive performances of preoperative CT findings were expressed in terms of sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) with pooled proportion. RESULTS: A total of 10 studies and 1,614 patients were included in this meta-analysis. Large volume ascites had the highest sensitivity (64%, CI 56-71%), with a PLR of 1.3 (CI 1.1-1.5) and an NLR of 0.73 (0.59-0.90), while lymph node involvement had the highest specificity (89%, CI 79-94%). The highest DOR of 3 (CI 2-4) was achieved in peritoneal involvement and large bowel mesentery involvement. The other CT findings had poorer predictive performance. CONCLUSION: Preoperative CT findings have a poor discriminative capacity to predict SCR in advanced OC. Preoperative CT predictors should be used with caution amid clinical decision-making.