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Abstract
BackgroundPin2/TRF1 binding protein X1 (PinX1) has been identified as an endogenous telomerase inhibitor and a major haploinsufficient tumor suppressor gene. Increasing evidence suggests that reduced expression of PinX1 plays a key role in tumorigenesis. However, the PinX1 expression status and its correlation with the clinicopathological features in prostate cancer (PCa) have not been investigated.MethodsPinX1 mRNA and protein expression in PCa and adjacent normal prostate tissues were evaluated by real-time quantitative RT-PCR (qRT-PCR) and western blotting. The clinicopathological significance of PinX1 was investigated by immunohistochemistry (IHC) analysis on a PCa tissue microarray (TMA). The cut-off score for positive expression of PinX1 was determined by the receiver operating characteristic (ROC) analysis. The correlation between PinX1 expression and clinicopathological features of PCa was analyzed by Chi-square test.ResultsReduced expression of PinX1 mRNA and protein was observed in the majority of PCa, compared with their paired adjacent normal prostate tissues. When PinX1 positive expression percentage was determined to be above 60% (area under ROC curve = 0.833, P = 0.000), positive expression of PinX1 was observed in 100% (8/8) of normal prostate tissues and 32.5% (13/40) of PCa tissues by IHC. Reduced expression of PinX1 in patients was correlated with advanced clinical stage (χ2 = 10.230, p = 0.017), high Gleason score (χ2 = 4.019, p = 0.045), positive regional lymph node metastasis (χ2 = 10.852, p = 0.004) and distant metastasis (χ2 = 7.965, p = 0.005).ConclusionsOur findings suggest that reduced expression of PinX1 is correlates to progressive features in patients with PCa and may serve as a potential marker for diagnosis.
Highlights
Pin2/TRF1 binding protein X1 (PinX1) has been identified as an endogenous telomerase inhibitor and a major haploinsufficient tumor suppressor gene
Expression of PinX1 mRNA and protein in paired prostate cancer (PCa) and adjacent normal prostate tissues The quantitative RT-PCR (qRT-PCR) result showed that in 14 of the 16 sample pairs, fold changes were less than 1 between PCa and adjacent normal prostate tissue (Figure 1A), which indicated the PinX1 mRNA expression was downregulated in PCa tissues compared to the adjacent normal prostate tissues
The receiver operating characteristic (ROC) curve for all the clinicopathological features at different PinX1 scope were plotted (Figure 3), the corresponding area under the ROC curve (AUC) and P-value were analyzed by the SPSS 13.0 software (Table 1)
Summary
Pin2/TRF1 binding protein X1 (PinX1) has been identified as an endogenous telomerase inhibitor and a major haploinsufficient tumor suppressor gene. The PinX1 expression status and its correlation with the clinicopathological features in prostate cancer (PCa) have not been investigated. Pin2/TRF1 binding protein X1 (PinX1) has been identified as an endogenous telomerase inhibitor and a major haploinsufficient tumor suppressor gene localized at human chromosome 8p23, a region with frequent loss of heterozygosity in a number of human cancers [6]. Zhou et al reported that PinX1 expression was reduced in most human breast cancer tissues and cell lines, PinX1 allele loss caused majority of mice to develop a variety of epithelial cancers, the mechanism involves chromosome instability which recapitulated to 8p23 allele loss in humans [7,8]. The PinX1 expression status and its correlation with the clinicopathological features in PCa have not been investigated
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