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Decreased HoxD10 Expression Promotes a Proliferative and Aggressive Phenotype in Prostate Cancer

[ Vol. 17 , Issue. 1 ]

Author(s):

R.-J. Mo, J-M Lu, Y.-P. Wan, W. Hua, Y.-X. Liang, Y.-J. Zhuo, Q.-W. Kuang, Y.-L. Liu, H.-C. He and W.-D. Zhong*   Pages 70 - 78 ( 9 )

Abstract:


HoxD10 gene plays a critical role in cell proliferation in the process of tumor development. However, the protein expression level and the function of HoxD10 in prostate cancer remain unknown. Using tissue microarray, we demonstrate that the protein expression of HoxD10 is commonly decreased in prostate cancer tissues (n = 92) compared to adjacent benign prostate tissues (n = 77). Functionally, knockdown of HoxD10 resulted in significant promotion of prostate cancer cell proliferation. Moreover, knockdown of HoxD10 strikingly stimulated prostate tumor growth in a mouse xenograft model. We also found a significant association between decreased immunohistochemical staining of HoxD10 expression and higher Gleason score (P = 0.031) and advanced clinical pathological stage (P = 0.011). An analysis of the Taylor database revealed that decreased HoxD10 expression predicted worse biochemical recurrence (BCR)-free survival of PCa patients (P = 0.005) and the multivariate analyses further supported that HoxD10 might be an independent predictor for BCR-free survival (P = 0.027). Collectively, our data suggest that the loss of HoxD10 function is common and may thus result in a progressive phenotype in PCa. HoxD10 may function as a biomarker that differentiates patients with BCR disease from the ones that are not after radical prostatectomy, implicating its potential as a therapeutic target.

Keywords:

Prostrate cancer, HoxD10 gene, immunohistochemistry, proliferation, aggressive phenotype, biochemical recurrence-free survival, progression.

Affiliation:

Department of Urology, Huadu District People's Hospital, Southern Medical University, Guangzhou 510800, Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, Guangzhou Medical University, Guangzhou 510180, Department of Urology, Huadu District People's Hospital, Southern Medical University, Guangzhou 510800, Department of Urology, Huadu District People's Hospital, Southern Medical University, Guangzhou 510800, Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, Guangzhou Medical University, Guangzhou 510180, Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, Guangzhou Medical University, Guangzhou 510180, Guangdong Provincial Institute of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, College of Agricultural and Environmental Sciences, University of California, Davis, CA 95616, Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, Guangzhou Medical University, Guangzhou 510180, Department of Urology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180



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