SOXs in human prostate cancer: implication as progression and prognosis factors.
BACKGROUND
SOX genes play an important role in a number of developmental processes. Potential roles of SOXs have been demonstrated in various neoplastic tissues as tumor suppressors or promoters depending on tumor status and types. The aim of this study was to investigate the involvement of SOXs in the progression and prognosis of human prostate cancer (PCa).


METHODS
The gene expression changes of SOXs in human PCa tissues compared with non-cancerous prostate tissues was detected using gene expression microarray, and confirmed by real-time quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) analysis and immunohositochemistry. The roles of these genes in castration resistance were investigated in LNCaP xenograft model of PCa.


RESULTS
The microarray analysis identified three genes (SOX7, SOX9 and SOX10) of SOX family that were significantly dis-regulated in common among four PCa specimens. Consistent with the results of the microarray, differential mRNA and protein levels of three selected genes were found in PCa tissues by QRT-PCR analysis and immunohistochemistry. Additionally, we found that the immunohistochemical staining scores of SOX7 in PCa tissues with higher serum PSA level (P = 0.02) and metastasis (P = 0.03) were significantly lower than those with lower serum PSA level and without metastasis; the increased SOX9 protein expression was frequently found in PCa tissues with higher Gleason score (P = 0.02) and higher clinical stage (P < 0.0001); the down-regulation of SOX10 tend to be found in PCa tissues with higher serum PSA levels (P = 0.03) and advanced pathological stage (P = 0.01). Moreover, both univariate and multivariate analyses showed that the down-regulation of SOX7 and the up-regulation of SOX9 were independent predictors of shorter biochemical recurrence-free survival. Furthermore, we discovered that SOX7 was significantly down-regulated and SOX9 was significantly up-regulated during the progression to castration resistance.


CONCLUSIONS
Our data offer the convince evidence that the dis-regulation of SOX7, SOX9 and SOX10 may be associated with the aggressive progression of PCa. SOX7 and SOX9 may be potential markers for prognosis in PCa patients. Interestingly, the down-regulation of SOX7 and the up-regulation of SOX9 may be important mechanisms for castration-resistant progression of PCa.
Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First Municipal People's Hospital, Affiliated Guangzhou Medical College, Guangzhou 510180, China. zhongwd2009@live.cn
Wei-de
WD
Zhong
Guo-qiang
GQ
Qin
Qi-shan
QS
Dai
Zhao-dong
ZD
Han
Shan-ming
SM
Chen
Xiao-hui
XH
Ling
Xin
X
Fu
Chao
C
Cai
Jia-hong
JH
Chen
Xi-bin
XB
Chen
Zhuo-yuan
ZY
Lin
Ye-han
YH
Deng
Shu-lin
SL
Wu
Hui-chan
HC
He
Chin-lee
CL
Wu
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D018450:Disease Progression; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009919:Orchiectomy; D011379:Prognosis; D011470:Prostatic Hyperplasia; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D015203:Reproducibility of Results; D055747:SOX Transcription Factors / Q000235:genetics* / Q000378:metabolism; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism; D055757:SOXE Transcription Factors / Q000235:genetics / Q000378:metabolism; D055760:SOXF Transcription Factors / Q000235:genetics / Q000378:metabolism
D055747:SOX Transcription Factors; C527923:SOX10 protein, human; C484456:SOX7 protein, human; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D055757:SOXE Transcription Factors; D055760:SOXF Transcription Factors