Abstract
Sineoculis homeobox homolog 1 (Six1), normally a developmentally restricted transcriptional regulator, is frequently dysregulated in mutiple cancers. Increasing evidences show that overexpression of Six1 plays a key role in tumorigenesis. However, the Six1 expression status and its relationship with the clinicopathological characteristics in prostate cancer were unclear. In this study, the mRNA and protein levels of Six1 in prostate cancer tissues and normal prostate tissues were evaluated. The clinicopathological significance of Six1 was investigated by immunohistochemistry (IHC) on a prostate cancer tissue microarray. The cut-off score for high expression of Six1 was determined by the receiver-operating characteristic (ROC) analysis. The correlation between Six1 protein expression and clinicopathological characteristics of prostate cancer was analyzed by Chi-square test. Increased expression of Six1 protein was observed in the majority of prostate cancer, compared with their paired adjacent normal prostate tissues. When Six1 high expression percentage was determined to be above 55 % (area under ROC curve = 0.881, P = 0.000), high expression of Six1 was observed in 55.6 % (80/144) of prostate cancer tissues and low expression of Six1 was observed in all normal prostate tissues by IHC. Increased expression of Six1 in patients was correlated with high histological grade (χ2 = 58.651, P = 0.00), advanced clinical stage (χ2 = 57.330, P = 0.000), high Gleason score (χ2 = 63.480, P = 0.000), high primary tumor grade (χ2 = 57.330, P = 0.000) and positive regional lymph node metastasis (χ2 = 19.294, P = 0.000). Furthermore, univariate and multivariate survival analysis suggested that Six1 was an independent prognostic indicator for overall survival (P < 0.05). This study suggests that Six1 could be served as an additional biomarker in identifying prostate cancer patients at risk of tumor progression, might potentially be used for predicting survival outcome of patients with prostate cancer.
Highlights
Current diagnosis for prostate cancer includes digital rectal examination (DRE), prostate-specific antigen (PSA) and needle biopsy [1]
The expression level of Sineoculis homeobox homolog 1 (Six1) in prostate cancer and adjacent normal prostate tissues detected by western blotting and IHC In this study, the protein and/or messenger RNA (mRNA) expression of Six1 was first examined by Western blotting and/or qRT-PCR in 8 pairs of primary prostate cancer and adjacent normal prostate tissues
A significantly increase in both protein and mRNA expression of Six1 was detected in prostate cancer tissues compared to adjacent nontumorous tissues (Fig. 1a and b)
Summary
Current diagnosis for prostate cancer includes digital rectal examination (DRE), prostate-specific antigen (PSA) and needle biopsy [1]. The appearance of prostate-specific antigen (PSA) testing has revolutionarily improved early prostate cancer detection. If rising PSA levels are detected, a needle biopsy of the prostate is recommended to inspect for histologic evidence of prostate cancer. Current reports have raised concern over the efficacy of PSA testing. The U.S prostate cancer screening trial report found that the mortality caused by prostate cancer was not reduced by PSA screening [2].
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