SOXs in human prostate cancer: implication as progression and prognosis factors

Abstract

BackgroundSOX 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).MethodsThe 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.ResultsThe 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.ConclusionsOur 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.

Expression and Clinical Significance of SOX9 in Renal Cell Carcinoma, Bladder Cancer and Penile Cancer

“…Recent studies have shown the involvement of upregulated SOX9 in several cancer types [5,[10][11][12][13], including lung adenocarcinoma, breast carcinoma, colorectal cancer, and PCa. Furthermore, our previous study reported the association of increased serum level of SOX9 with aggressive tumor progression and poor prognosis in PCa patients, thereby suggesting its potential as a serological tumor marker for PCa [14,15]. However, the clinical and functional significance of SOX9 expression has not yet been characterized in other urological cancers.…”

Sox10 expression in ovarian epithelial tumors is associated with poor overall survival

“…Similarly, Sox10 was found downregulated in prostate carcinoma tissue compared to benign prostate tissue. In prostate carcinoma, low immunoreactivity of Sox10 was associated with high PSA level and advanced pathological stage [19]. Clearly, the role of Sox10 in oncogenesis of epithelial tumors needs to be further elucidated.…”

“…Sox10 reportedly functions as an oncogene by cell cycle dysregulation in melanomagenesis [18], and by activating the Wnt/β-catenin cascade in hepatocellular carcinoma [17]. In contrast, Sox10 is silenced or downregulated in prostatic carcinoma [19] and in gastrointestinal cancer [20], suggesting that in these tumors, it might function as a tumor suppressor.…”

A Newly Developed Mouse Monoclonal SOX10 Antibody Is a Highly Sensitive and Specific Marker for Malignant Melanoma, Including Spindle Cell and Desmoplastic Melanomas

“…In the study by Mohamed et al, 1 nonspecific background staining was observed in photomicrographs in both melanoma and in breast cancer. In a study by Zhong et al, 19 SOX10 was strongly positive in the cytoplasm of benign prostate tissue and was weakly positive in the cytoplasm of prostate cancer tissues. In our study, the new monoclonal SOX10 antibody produced clean nuclear staining with essentially no background staining.…”

“…1,[10][11][12][13][14][15]19 The use of a research use-only goat primary antibody may be satisfactory for research purposes; however, it may not be generally accepted in a clinical setting. Polyclonal antibodies are also notorious for lot-to-lot variation and may produce unwanted nonspecific background staining.…”