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已发表论文
三阴乳腺癌的 ETV4 蛋白过度表达与较高风险的远处转移相关
Authors Yuan ZY, Dai T, Wang SS, Peng RJ, Li XH, Qin T, Song LB, Wang X
Published Date September 2014 Volume 2014:7 Pages 1733—1742
DOI http://dx.doi.org/10.2147/OTT.S66692
Received 23 April 2014, Accepted 6 August 2014, Published 26 September 2014
Approved for publication by Dr Faris Farassati
Background: Patients with triple-negative breast cancer (TNBC) present a higher probability of distant metastasis and lack of effective targeted therapy. ETS trans variant 4 (ETV4) is an ETS (E-26) transcription factor and has been associated with tumor metastasis. However, the clinical and functional significance of ETV4 in TNBC still remains unclear.
Methods: A human tumor metastasis polymerase chain reaction array was used to profile differential expression of tumor metastasis-related genes in TNBC tissue. Real-time reverse transcription and Western blot analyses were performed to verify ETV4 expression in TNBC cells and tissue. Immunohistochemistry was used to detect expression of ETV4 protein in 135 TNBC tissue samples for association between ETV4 protein expression and clinical outcomes.
Results: A total total of eight upregulated (CCL7 , KISS1 , MET , MMP7 , NR4A3 , ETV4 , TIMP3 , and TSHR ) and three downregulated (ITGA7 , SSTR , and MMP2 ) genes were identified between TNBC tissue and the luminal subtype of breast cancer tissue. ETV4 messenger ribonucleic acid was more than five-fold upregulated in TNBC tissue compared with the control tissue. ETV4 overexpression was found in 57.0% of 135 TNBC cases. Overexpression of ETV4 protein was associated with an advanced stage and a higher proportion of positive lymph node and lymphovascular invasion. Patients with an ETV4-overexpressed tumor had a significantly higher risk of developing distant metastasis (P <0.0001) and shorter overall survival and disease-free survival. Overexpression of ETV4 protein was an independent predictor of short disease-free survival of TNBC patients (P =0.021).
Conclusion: Overexpression of ETV4 protein increases risk of developing distant metastasis and results in a poor prognosis for TNBC patients. Thus, ETV4 might be a novel target for developing an alternative therapeutic strategy for prevention of TNBC distant metastasis.
Keywords: breast carcinoma, triple-negative, ETS trans variant 4, ETV4, prognosis
Methods: A human tumor metastasis polymerase chain reaction array was used to profile differential expression of tumor metastasis-related genes in TNBC tissue. Real-time reverse transcription and Western blot analyses were performed to verify ETV4 expression in TNBC cells and tissue. Immunohistochemistry was used to detect expression of ETV4 protein in 135 TNBC tissue samples for association between ETV4 protein expression and clinical outcomes.
Results: A total total of eight upregulated (CCL7 , KISS1 , MET , MMP7 , NR4A3 , ETV4 , TIMP3 , and TSHR ) and three downregulated (ITGA7 , SSTR , and MMP2 ) genes were identified between TNBC tissue and the luminal subtype of breast cancer tissue. ETV4 messenger ribonucleic acid was more than five-fold upregulated in TNBC tissue compared with the control tissue. ETV4 overexpression was found in 57.0% of 135 TNBC cases. Overexpression of ETV4 protein was associated with an advanced stage and a higher proportion of positive lymph node and lymphovascular invasion. Patients with an ETV4-overexpressed tumor had a significantly higher risk of developing distant metastasis (P <0.0001) and shorter overall survival and disease-free survival. Overexpression of ETV4 protein was an independent predictor of short disease-free survival of TNBC patients (P =0.021).
Conclusion: Overexpression of ETV4 protein increases risk of developing distant metastasis and results in a poor prognosis for TNBC patients. Thus, ETV4 might be a novel target for developing an alternative therapeutic strategy for prevention of TNBC distant metastasis.
Keywords: breast carcinoma, triple-negative, ETS trans variant 4, ETV4, prognosis
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