Xue-cheng Bi

CD147, MMP-1, MMP-2 and MMP-9 Protein Expression as Significant Prognostic Factors in Human Prostate Cancer

Aim: CD147 and MMPs have been demonstrated to be involved in tumor invasion and angiogenesis. The aim of this study was to analyze the clinicopathological significance of CD147, MMP-1, MMP-2 and MMP-9 expression in human prostate cancer (PCa) and to evaluate their involvement in the progression of PCa. Methods: CD147, MMP-1, MMP-2 and MMP-9 expression was assessed in paraffin-embedded specimens collected from 62 cases of PCa and 15 cases of benign prostatic hyperplasia (BPH) by immunohistochemistry. Spearman’s correlation was applied to determine possible relationships between CD147, MMP-1, MMP-2 and MMP-9 expression and PCa. The association of CD147 and MMP-2 protein expression with the clinicopathological characteristics and the prognosis of PCa was subsequently assessed. Results: CD147was expressed in 51/62 (82.3%) PCa patients and in 2/15 (13.3%) BPH cases. MMP-1, MMP-2 and MMP-9 expression was significantly higher in PCa tissue than in BPH tissue. Using Spearman analysis, a significant positive correlation between CD147 and MMP-1, MMP-2 and MMP-9 expression was found (p <0.05). CD147 and MMP-2 expression was correlated with TMN grade and Gleason score. Patients with concurrent expression of CD147+ and MMP-2+ had the lowest survival (p <0.01). Conclusion: The results suggest that concurrent expression of CD147 and MMP may be an important characteristic of PCa which may help in the prediction of PCa progression.

CD147 and VEGF Expression in Advanced Renal Cell Carcinoma and Their Prognostic Value

Aim: To investigate the clinicopathologic characteristics of extracellular matrix (ECM) metalloproteinase inducer (CD147) and vascular endothelial growth factor (VEGF) expression in advanced renal cell carcinoma (RCC), and to evaluate the clinical significance of these two markers in the prognosis of advanced RCC. Methods: CD147 and VEGF expression in paraffin-embedded specimens gathered from 53 patients with advanced RCC and 12 healthy controls were detected by the method of immunohistochemistry. The Spearman correlation was calculated between the expression levels of CD147 and VEGF in advanced RCC tissues. The association of CD147 and VEGF expression with the clinicopathologic features and prognosis of advanced RCC was subsequently assessed. Results: CD147 and VEGF were positively expressed in 47/53 (88.7%) and 45/53 (84.9%) of patients with advanced RCC, respectively. Positive expression of CD147 (p= 0.02) and VEGF (p< 0.01) was significantly correlated with TNM stage of advanced RCC. A significant correlation was found between the expression of CD147 and VEGF in advanced RCC (r= 0.629, p= 0.04). Additionally, tumor CD147 and tumor VEGF expressions were significantly associated with the prognosis of advanced RCC patients. The survival rate of the patients with CD147−/VEGF− expression was the lowest (p< 0.01), and conjoined expressions of CD147−/VEGF− and CD147+/VEGF+ were independent prognostic indicators of advanced RCC (both p< 0.01). Conclusion: The expression of CD147 or VEGF may be an important feature of advanced RCC. A combined detection of CD147/VEGF coexpression may benefit us in the prediction of the prognosis of advanced RCC.

CD147 expression indicates unfavourable prognosis in prostate cancer.

Extracellular matrix metalloproteinase inducer (EMMPRIN, also named as CD147) is a multifunctional membrane glycoprotein over-expressed in many kinds of human solid tumors. It has been demonstrated to be involved in tumor invasion and angiogenesis. The aim of this study was to analyze the clinicopathological characteristics of the expression of CD147 in human prostate cancer (PCa), and to evaluate its clinical significance in the histologic classification and prognosis of PCa. CD147 protein expression in paraffin-embedded specimens gathered from 62 cases of PCa and 30 cases of benign prostatic hyperplasia (BPH) were detected by the method of immunohistochemistry. The association of CD147 protein expression with the clinicopathological characteristics and with the prognosis of PCa was subsequently assessed. CD147 expression were positively expressed in 51/62 (82.3%) of PCa and 4/30 (13.3%) of BPH cases, respectively. The positive expression rate of CD147 in PCa tissues was significantly higher than that in BPH. The positive expression of CD147 was dramatically associated with TNM grade (p < 0.001), the depth of the prostatic wall invasion (p = 0.008), GLEASON Score (p = 0.001) and Histologic grade (p = 0.001). The patients with CD147 expression were associated with a poor prognosis of PCa (p = 0.01) and the survival rate of the patients with a strong positive expression of CD147 was the lowest (p = 0.01). The results suggest that the expression of CD147 may be an important feature of PCa and the detection of its expression may benefit us in the prediction of the prognosis of PCa.

Expression of CD147 is associated with prostate cancer progression

Novel molecular markers that are associated with prostate cancer (PCa) progression will provide valuable information in the diagnosis and treatment of the disease. Extracellular matrix metalloproteinase inducer (CD147) has been demonstrated to be involved in tumor invasion, metastasis, growth and survival. In our study, we examined whether the expression of CD147 can be used as a prognostic marker for predicting PCa progression. Tissue samples from 240 patients who received radical prostatectomy for PCa were obtained. CD147 expression in these samples was evaluated using immunohistochemical staining with a monoclonal antibody specifically against CD147. Increased expression of CD147 was correlated with higher Gleason scores (GS), positive surgical margin, prostate‐specific antigen (PSA) failure, metastasis and reduced overall survival. Both univariate Cox regression analysis and multivariate analysis including competing biological variables demonstrated that increased CD147 expression was associated with increased risk for reduced PSA failure‐free, metastasis‐free and overall survival. Kaplan–Meier survival curves showed that the CD147 overexpression was a significant predictor for the PSA failure‐free, metastasis‐free and the overall survival in both pT2 and pT3 PCa patients. More significantly, higher expression of CD147 can serve as an independent prognostic predictor for PSA failure‐free survival in PCa patients when they are stratified by GS. Our study results demonstrate the involvement of CD147 in PCa progression and suggest its potential role as an independent predictor of biochemical recurrence, development of metastasis and reduced overall survival in PCa.

Inhibition of proliferation, invasion, and migration of prostate cancer cells by downregulating elongation factor-1alpha expression.

Overexpression of elongation factor-1α (EF-1α) has been reported to contribute to the development and progression of various cancers. However, its role in prostate cancer (PCa) still remains poorly understood. In the present study, we investigate the influence of EF-1α in Du145, a high-grade metastatic PCa cell line, and demonstrate that EF-1α plays an essential role in cellular properties associated with tumor progression, namely cell proliferation, invasion, and migration. In this study, EF-1α expression in human PCa cell line Du145 was reduced by RNA interference (RNAi) technology, and the proliferation, invasion, and migration of EF-1α-reduced Du145 cells were examined. We also detected an EF-1α expression pattern in 20 pairs of primary PCa samples and their corresponding normal tissues. Expression of EF-1α was detectable in four PCa cell lines (22RV1, LnCap, Du145, and PC3), indicating its possible role in pathogenesis of PCa. RNAi-mediated knockdown of EF-1α expression in Du145 cells, which expressed the highest level of EF-1α among four PCa cell lines, led to a decrease in proliferation. Similarly, suppression of EF-1α inhibited Du145 cell migration and invasion through a basement membrane substitute. Furthermore, we found that the normal prostate tissues showed a relatively low level of EF-1α expression, whereas PCa tissues demonstrated significantly higher expression levels of EF-1α (P < 0.001). Taken together, these findings support the hypothesis that EF-1α affects multiple processes involved in tumor progression, and identify EF-1 a as a potential therapeutic target.

Extracellular matrix metalloproteinase inducer expression has an impact on survival in human bladder cancer.

AIM Extracellular matrix metalloproteinase inducer (EMMPRIN) has been shown to promote tumor invasion and metastasis via stimulating matrix metalloproteinase synthesis in neighboring fibroblasts, to enhance angiogenesis via vascular endothelial growth factor, to induce chemoresistant tumor cells via the production of hyaluronan, and to confer resistance of cancer cells to anoikis through inhibition of Bim. The purpose of this study was to investigate the expression of EMMPRIN in human primary bladder cancer and to evaluate its prognostic value. METHODS EMMPRIN expression patterns were detected by immunohistochemistry. In order to determine its prognostic value, overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method, and multivariate analysis was performed using the Cox proportional hazard analysis. RESULTS Of the 101 cases with bladder cancers, 68 (67.3%) cases were positive for EMMPRIN expression. When categorized into negative vs. positive expression, EMMPRIN was associated with the stage (p=0.006), the grade (p=0.002), carcinoma in situ (p=0.01), the recurrence (p=0.009), the progression (p=0.009), and the death (p=0.01) of patients with bladder cancer. Moreover, positive EMMPRIN expression clearly predicted poorer PFS (p=0.008) and OS (p=0.006). In the multivariate analysis, positive EMMPRIN expression was an independent prognostic factor for PFS (p=0.03) and OS (p=0.03). CONCLUSION EMMPRIN expression was greater in bladder cancers than in the adjacent normal tissues and may be a useful prognostic marker for patients with bladder cancer.

Pathogen Incidence and Antibiotic Resistance Patterns of Catheter-Associated Urinary Tract Infection in Children

Abstract The aim of this study was to characterize the pathogens and their antibiotic susceptibilities in children with catheter-associated urinary tract infection (CAUTI) in order to optimize empirical antibiotic therapy and prophylaxis. From 2001 to 2006, 895 children with an indwelling catheter from 3 hospitals in China were included in this study, of whom 335 (37.4%) had CAUTI. Antimicrobial susceptibility testing of 450 bacterial isolates was performed using the CLSI broth and Kirby-bauer agar dilution methods. Escherichia coli was the most frequently isolated pathogen, followed by Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus spp. E. coli had higher susceptibility to ceftazidime (87.4%), cefuroxime (85.1%) and cefatrizine (76.6%) than to sulfamethoxazole (SMZ) (8.0%), amoxicillin (21.7%), ampicillin (17.1%) and cefazolin (37.7%). Isolates of Klebsiella pneumoniae and Proteus species had similar patterns as E. coli. S. aureus had lower susceptibility to SMZ (6.8%), ampicillin (8.2%), and amoxicillin (24.7%); the trend of S. epidermidis was similar. This study demonstrates that the Gram-negative species are the predominating uropathogens of CAUTI in children. it is important to know the bacterial spectrum and the susceptibility patterns to various classes of antibiotic agents to improve empiric antibiotic therapy of children with CAUTI in China.