title: Decreased HoxD10 Expression Promotes a Proliferative and Aggressive Phenotype in Prostate Cancer.
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.
authors.affiliation: Department of Urology, Huadu District People's Hospital, Southern Medical University, Guangzhou 510800. China.
authors.forename: R-J
authors.initials: RJ
authors.lastname: Mo
authors.affiliation: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180. China.
authors.forename: J-M
authors.initials: JM
authors.lastname: Lu
authors.affiliation: Department of Urology, Huadu District People's Hospital, Southern Medical University, Guangzhou 510800. China.
authors.forename: Y-P
authors.initials: YP
authors.lastname: Wan
authors.affiliation: Department of Urology, Huadu District People's Hospital, Southern Medical University, Guangzhou 510800. China.
authors.forename: W
authors.initials: W
authors.lastname: Hua
authors.affiliation: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180. China.
authors.forename: Y-X
authors.initials: YX
authors.lastname: Liang
authors.affiliation: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180. China.
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Zhuo
authors.affiliation: Guangdong Provincial Institute of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou 510515. China.
authors.forename: Q-W
authors.initials: QW
authors.lastname: Kuang
authors.affiliation: College of Agricultural and Environmental Sciences, University of California, Davis, CA 95616. United States.
authors.forename: Y-L
authors.initials: YL
authors.lastname: Liu
authors.affiliation: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180. China.
authors.forename: H-C
authors.initials: HC
authors.lastname: He
authors.affiliation: Department of Urology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180. China.
authors.forename: W-D
authors.initials: WD
authors.lastname: Zhong
mesh_terms: D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D010641:Phenotype; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D034741:RNA, Small Interfering / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; D034741:RNA, Small Interfering; D014157:Transcription Factors; C072064:HOXD10 protein, human
keywords: HoxD10 gene; Prostrate cancer; aggressive phenotype; biochemical recurrence-free survival; immunohistochemistry; progression; proliferation