Decreased HoxD10 Expression Promotes a Proliferative and Aggressive Phenotype in Prostate Cancer
2017
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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