摘要
HoxD10基因在肿瘤细胞增殖进程中扮演了关键的角色。然而,蛋白质表达的等级和HoxD10在前列腺癌中的功能还未知。使用组织微列阵,我们证明了在前列腺癌组织中HoxD10蛋白质的表达普遍降低(n=92),与相邻的良性前列腺组织相比(n=77)。功能上说,击倒HoxD10导致前列腺癌细胞增生有极为重要的意义。其次,击倒HoxD10严格地刺激了前列腺肿块的生长在老鼠异种移植模型中。我们也发现一个关于降低HoxD10表达的免疫组织化学染色和高格里森评分(P=0.031)和临床方法学进程等级(P=0.011)之间有重要意义的关联。泰勒数据库的一个分析揭露了降低HoxD10表达预示更糟生化复发(BCR)-前列腺癌患者的无病生存期(P = 0.005)和多变量分析进一步证实HOXD10可能BCR无生存的独立预测因子(P = 0.027)。总的来说,我们的数据表示HoxD10功能丢失很普遍同时可能导致结果在PCA的渐进型。HoxD10可能作为一个生物标记,区分BCR病患者与那些不是根治性前列腺切除术后,暗示其潜在的治疗靶点。
关键词: 前列腺癌,HoxD10基因,免疫组织化学,增生,侵袭性表型,生化无复发生存、发展。
Current Molecular Medicine
Title:Decreased HoxD10 Expression Promotes a Proliferative and Aggressive Phenotype in Prostate Cancer
Volume: 17 Issue: 1
关键词: 前列腺癌,HoxD10基因,免疫组织化学,增生,侵袭性表型,生化无复发生存、发展。
摘要: 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.
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Decreased HoxD10 Expression Promotes a Proliferative and Aggressive Phenotype in Prostate Cancer, Current Molecular Medicine 2017; 17 (1) . https://dx.doi.org/10.2174/1566524017666170220104920
DOI https://dx.doi.org/10.2174/1566524017666170220104920 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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