Over-Expression of TBL1XR1 Indicates Poor Prognosis of Serous Epithelial Ovarian Cancer.
Transducin (β)-like 1 X-linked receptor 1 (TBL1XR1) is a core component of the NCoR/SMRT transcription co-repressor complex, and its role in regulating cancer progression has been reported. Serous epithelial ovarian cancer (EOC) is the most common histological type of EOC. Here we explored the significance of TBL1XR1 expression in predicting outcomes of patients with serous EOC. Real-time quantitative PCR analysis showed that the expression level of TBL1XR1 mRNA was significantly higher in EOC tissues compared with adjacent non-tumorous tissues. The protein levels of TBL1XR1 in EOC tissues were assessed by immunohistochemistry, and the patients were classified into low-expression group (n = 62) and high-expression group (n = 54) according to the immunoreactivity. Prognostic significance of TBL1XR1 was evaluated by univariate and multivariate analyses, showing that over-expression of TBL1XR1 was correlated with poor prognosis. In addition, TBL1XR1 was positively associated with the lymph node metastasis of EOC. Because vascular endothelial growth factor (VEGF)-C is known as a critical mediator of lymph node metastasis, we measured the expression level of VEGF-C mRNA in EOC tissues and thus identified a positive correlation between TBL1XR1 and VEGF-C mRNA levels. Subsequently, using human EOC cell lines, we showed that silencing of TBL1XR1 decreased VEGF-C expression, suggesting that TBL1XR1 may function as an upstream regulator of VEGF-C in EOC. Furthermore, the proliferation and invasion of EOC cells were inhibited by TBL1XR1 silencing. In conclusion, TBL1XR1 overexpression may be an unfavorable prognostic factor for EOC. We also suggest that the TBL1XR1-VEGF-C axis may determine the EOC progression.
Department of Oncology, Linyi People's Hospital.
Ming
M
Ma
Nina
N
Yu
D000077216:Carcinoma, Ovarian Epithelial; D049109:Cell Proliferation; D002470:Cell Survival; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis / Q000473:pathology; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics / Q000378:metabolism
D009687:Nuclear Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins; C473691:TBL1XR1 protein, human; D042582:Vascular Endothelial Growth Factor C