| Background and Objective:With an increasing incidence, prostate carcinoma is one of the most common malignant tumor of urology system. Surgical intervention or hormonal therapy is the major available treatment for prostate carcinoma. Although temporarily effective, these treatments can not reduce the high rate of cancer relapse and increase the survival. The pathogenesis mechanism remain unclear, however, several genetic regulationary patterns invoke in the progression of carcinoma, involved in the dysregulation of the structure or expression of coding genes and non-coding genes. Recent studies elucidate that microRNA (miRNA), as a class of small non-coding RNAs, affect the special protein expression by post-transcriptional regulation mechanism and be associated with tumorigenesis and progression. In this study we examine the alterations of miRNA-203 (miR-203), P63, YKL-40 and Survivin protein expression in different prostate tissues to investigate the roles on prostate carcinoma progression and evaluate the patients'postoperative survival.Methods:In this study, formaldehyde-fixed, paraffin-embedded (FFPE) specimens from 56 patients with prostate carcinoma (PCa) and 10 patients with benign prostatic hyperplasia (BPH), obtained from the First Affiliated Hospital of Shanxi Medical University between 2003 and 2008, were collected and followed up. To verify the morphologic diagnosis, the routine H&E-stained sections and Gleason grading system were reviewed. The expression of miR-203 and P63 protein in 30 cases of PCa and 10 cases of BPH were detected by Real-time PCR and En Vision respectively, and the protein expression of YKL-40 and Survivin were investigated by immunohistochemistry using En Vision method. The relationships with the clinicopathological parameters were also analyzed. The association between the level of miR-203 and P63 protein expressison in different prostate tissues was analyzed by Spearman rank correlation. Kaplan-Meier and Multivariate Cox proportional hazards regression model analysis were applied to compare the survival curves and screen the independent prognosis factors respectively. Statistical analysis was performed using the SPSS 13.0 software package.Results:1. Between the prostate carcinoma and BPH tissues, there were significant differences in the expression of miR-203 (P<0.05). With Gleason score getting higher, the levels of miR-203 expression were up-regulated gradually. The fold changes between BPH and GS 7-8, BPH and GS 9-10, GS<7 and GS 7-8, GS<7 and GS 9-10 were 2.8,3.1,2.7,2.9, respectively. However, there was no significant difference between BPH and GS<7, GS7-8 and GS9-10(P>0.05).2. With respect to the clinical stage, there were significant differences in the expression of miR-203(P<0.05), and the levels of miR-203 expression with advanced stage were higher markedly than that with early stage. The fold changes between stage D and BPH, stage A, stage B. stage C were 3.8,8.7,2.4,1.7, respectively.3. The expression of miR-203 was related to bone metastasis (P<0.05), but not related to the serum total PSA levels and relapse (P>0.05). The level of miR-203 expression with bone metastasis was increased 1.9-fold than that without bone metastasis.4. In all BPH cases, the expression of P63 protein was positive. In 27 out of 30 prostate carcinoma cases, P63 protein was lost, and in other 3 cases, P63 protein was weakly positive. Spearman rank correlation results indicated that the level of miR-203 expression correlated negatively with P63 protein expression (r=-0.449, P<0.05).5. In cases with prostate carcinoma, the positive expression rates of YKL-40 and Survivin were 73.21%and 80.36%respectively, and positively correlated(r= 0.480, P<0.05). The positive expression of YKL-40 and Survivin were closely related to the Gleason grade and bone metastasis (P<0.05).6. Survival anlysis showed that the patients'survival time was significantly reduced in cases of patients with elavated expression of miR-203, YKL-40 and Survivin (P<0.05). Multivariate Cox proportional hazards regression model analysis indicated that miR-203, Gleason score and YKL-40 were independent prognosis factors in prostate carcinoma.Conclusion:1. Real-time PCR showed that the expression of miR-203 was up-regulated in the prostate carcinoma, and the elevated trendency accompanied with the malignant degree of tumor tissues. These evidences revealed that miR-203 may act as an oncogenetic miRNA in the pathgenesis of prostate carcinoma.2. The expression of P63 protein was positive in BPH tissues, but loss expression in prostate carcinoma. The elevated alteration of miR-203 level paralleled the loss expression of P63 protein to some extent in prostate tissues, which suggest that miR-203 may be one of the regulational mechanisms in the prostate carcinoma progression.3. The elevated expression of miR-203, YKL-40 and Survivin were related to Gleason score, clinical stage and bone metastasis, which suggest that these molecules affect the malignant outcome and tumor invasion in prostate carcinoma.4. Gleason score, bone metastasis, miR-203, YKL-40 and Survivin were associated with the patients'postoperative survival. These molecular markers applied to evaluate the patients' prognosis were useful to increase the survival rate and improve patients'survival quality.
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