Prediction of Ki-67 expression in bladder cancer based on CT radiomics nomogram.

Objectives: This study aimed to create and validate a radiomics nomogram for non-invasive preoperative Ki-67 expression level prediction in patients with bladder cancer (BCa) using contrast-enhanced CT radiomics features. Methods: A retrospective analysis of 135 patients was conducted, 79 of whom had high levels of Ki-67 expression and 56 of whom had low levels. For the dimensionality reduction analysis, the best features were chosen using the least absolute shrinkage selection operator and one-way analysis of variance. Then, a radiomics nomogram was created using multiple logistic regression analysis based on radiomics features and clinical independent risk factors. The performance of the model was assessed using the Akaike information criterion (AIC) value, the area under the curve (AUC) value, accuracy, sensitivity, and specificity. The clinical usefulness of the model was assessed using decision curve analysis (DCA). Results: Finally, to establish a radiomics nomogram, the best 5 features were chosen and integrated with the independent clinical risk factors (T stage) and Rad-score. This radiomics nomogram demonstrated significant correction and discriminating performance in both the training and validation sets, with an AUC of 0.836 and 0.887, respectively. This radiomics nomogram had the lowest AIC value (AIC = 103.16), which was considered to be the best model. When compared to clinical factor model and radiomics signature, DCA demonstrated the more value of the radiomics nomogram. Conclusion: Enhanced CT-based radiomics nomogram can better predict Ki-67 expression in BCa patients and can be used for prognosis assessment and clinical decision making.

Upregulation of BMP1 through ncRNAs correlates with adverse outcomes and immune infiltration in clear cell renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) accounts for approximately 2-3% of all adult malignancies. Clear cell renal cell carcinoma (ccRCC), which comprises 70-80% of all RCC cases, is the most common histological subtype. METHODS: ccRCC transcriptome data and clinical information were downloaded from the TCGA database. We used the TCGA and GEPIA databases to analyze relative expression of BMP1 in various types of human cancer. GEPIA was used to perform survival analysis for BMP1 in various cancer types. Upstream binding miRNAs of BMP1 were obtained through several important target gene prediction tools. StarBase was used to predict candidate miRNAs that may bind to BMP1 and candidate lncRNAs that may bind to hsa-miR-532-3p. We analyzed the association between expression of BMP1 and immune cell infiltration levels in ccRCC using the TIMER website. The relationship between BMP1 expression levels and immune checkpoint expression levels was also investigated. RESULTS: BMP1 was upregulated in GBM, HNSC, KIRC, KIRP and STAD and downregulated in KICH and PRAD. Combined with OS and DFS, BMP1 can be used as a biomarker for poor prognosis among patients with KIRC. Through expression analysis, survival analysis and correlation analysis, LINC00685, SLC16A1-AS1, PVT1, VPS9D1-AS1, SNHG15 and the CCDC18-AS1/hsa-miR-532-3p/BMP1 axis were established as the most potential upstream ncRNA-related pathways of BMP1 in ccRCC. Furthermore, we found that BMP1 levels correlated significantly positively with tumor immune cell infiltration, biomarkers of immune cells, and immune checkpoint expression. CONCLUSION: Our results demonstrate that ncRNA-mediated high expression of BMP1 is associated with poor prognosis and tumor immune infiltration in ccRCC.

A CT-based radiomics nomogram for differentiation of benign and malignant small renal masses (≤4 cm).

RATIONALE AND OBJECTIVES: Based on radiomics signature and clinical data, to develop and verify a radiomics nomogram for preoperative distinguish between benign and malignant of small renal masses (SRM). MATERIALS AND METHODS: One hundred and fifty-six patients with malignant (n = 92) and benign (n = 64) SRM were divided into the following three categories: category A, typical angiomyolipoma (AML) with visible fat; category B, benign SRM without visible fat, including fat-poor angiomyolipoma (fp-AML), and other rare benign renal tumors; category C, malignant renal tumors. At the same time, one hundred and fifty-six patients included in the study were divided into the training set (n = 108) and test set (n = 48). Respectively from corticomedullary phase (CP), nephrogram phase (NP) and excretory phase (EP) CT images to extract the radiomics features, and the optimal features were screened to establish the logistic regression model and decision tree model, and computed the radiomics score (Rad-score). Demographics and CT findings were evaluated and statistically significant factors were selected to construct a clinical factors model. The radiomics nomogram was established by merging Rad-score and selected clinical factors. The Akaike information criterion (AIC) values and the area under the curve (AUC) were used to compare model discriminant performance, and decision curve analysis (DCA) was used to assess clinical usefulness. RESULTS: Seven, fifteen, nineteen, and seventeen distinguishing features were obtained in the CP, NP, EP, and three-phase joint, respectively, and the logistic regression and decision tree models were built based on this features. In the training set, the logistic regression model works better than the decision tree model for distinguishing categories A and B from category C, with the AUC of CP, NP, EP and three-phase joint were 0.868, 0.906, 0.937 and 0.975, respectively. The radiomics nomogram constructed based on the three-phase joint Rad-score and selected clinical factor performed well on the training set (AUC, 0.988; 95% CI, 0.974-1.000) for differentiation of categories A and B from category C. In the test set, the AUC of clinical factors model, radiomics signature and radiomics nomogram for discriminating categories A and B from category C were 0.814, 0.954 and 0.968, respectively; for the identification of category A from category C, the AUC of the three models were 0.789, 0.979, 0.985, respectively; for discriminating category B from category C, the AUC of the three models were 0.853, 0.915, 0.946, respectively. The radiomics nomogram had better discriminative than the clinical factors model in both training and test sets (P < 0.05). The radiomics nomogram (AIC = 40.222) with the lowest AIC value was considered the best model compared with that of the clinical factors model (AIC = 106.814) and the radiomics signature (AIC = 44.224). The DCA showed that the radiomics nomogram have better clinical utility than the clinical factors model and radiomics signature. CONCLUSIONS: The logistic regression model has better discriminative performance than the decision tree model, and the radiomics nomogram based on Rad-score of three-phase joint and clinical factors has a good predictive effect in differentiating benign from malignant of SRM, which may help clinicians develop accurate and individualized treatment strategies.

CT-based deep learning radiomics signature for the preoperative prediction of the muscle-invasive status of bladder cancer.

Objectives: Although the preoperative assessment of whether a bladder cancer (BCa) indicates muscular invasion is crucial for adequate treatment, there currently exist some challenges involved in preoperative diagnosis of BCa with muscular invasion. The aim of this study was to construct deep learning radiomic signature (DLRS) for preoperative predicting the muscle invasion status of BCa. Methods: A retrospective review covering 173 patients revealed 43 with pathologically proven muscle-invasive bladder cancer (MIBC) and 130 with non-muscle-invasive bladder cancer (non- MIBC). A total of 129 patients were randomly assigned to the training cohort and 44 to the test cohort. The Pearson correlation coefficient combined with the least absolute shrinkage and selection operator (LASSO) was utilized to reduce radiomic redundancy. To decrease the dimension of deep learning features, Principal Component Analysis (PCA) was adopted. Six machine learning classifiers were finally constructed based on deep learning radiomics features, which were adopted to predict the muscle invasion status of bladder cancer. The area under the curve (AUC), accuracy, sensitivity and specificity were used to evaluate the performance of the model. Results: According to the comparison, DLRS-based models performed the best in predicting muscle violation status, with MLP (Train AUC: 0.973260 (95% CI 0.9488-0.9978) and Test AUC: 0.884298 (95% CI 0.7831-0.9855)) outperforming the other models. In the test cohort, the sensitivity, specificity and accuracy of the MLP model were 0.91 (95% CI 0.551-0.873), 0.78 (95% CI 0.594-0.863) and 0.58 (95% CI 0.729-0.827), respectively. DCA indicated that the MLP model showed better clinical utility than Radiomics-only model, which was demonstrated by the decision curve analysis. Conclusions: A deep radiomics model constructed with CT images can accurately predict the muscle invasion status of bladder cancer.

Long non-coding RNA (FALEC) promotes malignant behaviors of gastric cancer cells by regulating miR-203b/PIM3 axis.

Background: Existing research shows that long non-coding RNAs (lncRNAs) have important regulatory effects in gastric cancer (GC). In recent years, focally amplified lncRNA on chromosome 1 (FALEC) has been repeatedly reported to have carcinogenic effects in thyroid carcinoma, colorectal cancer, and endometrial cancer, etc. While the role and mechanism of FALEC during GC tumorigenesis remains unclear. Methods: The levels of FALEC, microRNA-203b (miR-203b), and Recombinant Pim-3 Oncogene (PIM3) were confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Cell autophagy, proliferation, apoptosis, migration, and invasion were estimated using western blot, transmission electron microscopy (TEM), cell counting kit-8 (CCK-8), flow cytometer, and Transwell assays. The interaction between miR-203b and FALEC or PIM3 was verified using a dual-luciferase reporter assay. Moreover, the involvement of miR-203b and PIM3 in the regulatory effects of FALEC on GC was determined with rescue experiments. Results: The results showed that FALEC and PIM3 were highly expressed, while miR-203b was lowly expressed, in GC. FALEC knockdown repressed GC cell proliferation, migration, and invasion, and promoted apoptosis and autophagy in vitro. Meanwhile, FALEC knockdown prevented growth and induced GC autophagy in vivo. This shows that FALEC upregulated PIM3 by sponging miR-203b in GC cells. Besides, FALEC induced the malignant behaviors of GC cells by regulating the miR-203b/PIM3 axis. Conclusions: The FALEC/miR-203b/PIM3 axis might be a promising therapeutic target for therapy in GC patients.

OIP5 Is a Novel Prognostic Biomarker in Clear Cell Renal Cell Cancer Correlating With Immune Infiltrates.

Opa interacting protein 5 (OIP5), overexpressed in some types of human cancers, has been reported to be associated with the carcinogenesis of human cancer. However, its contribution to cancer immunity remains unknown. Furthermore, the relationship between OIP5 and cancer immunity remains uncertain. In our research, we explored the different expression of OIP5 between 539 ccRCC and 72 normal renal tissues base on TCGA data set. We analyzed the associations between OIP5 expression with ccRCC progression and survival. Next, we compared immune cell profiles in cancer tissues and normal tissues in the Cancer Genome Atlas (TCGA) ccRCC cohort. We found that the level of immune cell infiltration was correlated with the copy number of OIP5 gene in ccRCC. The effect of OIP5 on immune activity was verified by Gene Set Enrichment Analysis of RNA-seq data from 32 ccRCC cell lines in the public database. Moreover, a pathway enrichment analysis of 49 OIP5-associated immunomodulators demonstrated the involvement of the T cell receptor signaling pathway, the JAK-STAT signaling pathway, the NF-kappa B signaling pathway and the primary immunodeficiency pathway. In addition, using OIP5-associated immunomodulators, we constructed multiple-gene risk prediction signatures using the Cox regression model. Our results provided insights into the role of OIP5 in tumor immunity and revealed that OIP5 may be a potential immunotherapeutic target for ccRCC. Designated immune signature is a promising prognostic biomarker in ccRCC.

Enhanced Expression of CNTD2/CCNP Predicts Poor Prognosis in Bladder Cancer Based on the GSE13507.

Bladder cancer is one of the most common urogenital malignancies in the world, and there are no adequate prognostic indicators. CNTD2 is one of the atypical cyclins, which may be related to the cell cycle and even the development of cancers. Early studies have shown that CNTD2 is closely related to the occurrence and development of many malignant tumors. However, the mechanism of CNTD2 in bladder cancer has not been reported. In our research, we explored the different expressions of CNTD2 between 411 bladder cancers and 19 normal bladder tissues based on the TCGA dataset. CNTD2-related signaling pathways were identified through the GSEA. We analyzed the associations of CNTD2 expression and bladder cancer progression and survival using GSE13507. Compared with 19 cases of normal bladder tissue, CNTD2 gene expression was increased in 411 cases of bladder cancer. The high expression of CNTD2 strongly correlated with grade (P < 0.0001), T classification (P = 0.0001), N classification (P = 0.00011), M classification (P = 0.044), age (P = 0.027), and gender (P = 0.0012). Bladder cancer patients with high CNTD2 expression had shorter overall survival (P < 0.001). In the meantime, univariate and multivariate analyses showed that the increased expression of CNTD2 was an independent factor for poor prognosis in bladder cancer patients (P < 0.001 and P < 0.001, respectively). CNTD2 expression is closely related to bladder cancer progression, and the high expression of CNTD2 may be an adverse biomarker in bladder cancer patients.

Identification of potential crucial genes associated with carcinogenesis of clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a common genitourinary malignancy with high mortality. However, the molecular pathogenesis of ccRCC remains unclear and effective biomarkers for daily practice are still limited. Thus, we aimed to identify the potential crucial genes and pathways associated with carcinogenesis of ccRCC and further analyze the molecular mechanisms implicated in tumorigenesis. In the present study, expression profiles GSE 66270, GSE 53757, GSE 36895, and GSE 76351 were downloaded from GEO database, including 244 matched primary and adjacent normal tissues, furthermore, the level 3 RNAseq dataset (RNAseqV2 RSEM) of KIRC was also downloaded from The Cancer Genome Atlas (TCGA), which consist of 529 ccRCC tumors and 72 normal tissues. Then, differentially expressed genes (DEGs) and pathway enrichment were analyzed by using R software. A total of 129 up- and 123 down-regulated genes were identified, which were aberrantly expressed both in GEO and TCGA data. Second, Gene ontology (GO) analyses revealed that most of the DEGs were significantly enriched in integral component of membrane, extracellular exosome, plasma membrane, cell adhesion, and receptor binding. Signaling pathway analyses indicated that DEGs had common pathways in signal transduction, metabolism, and immune system. Third, hub genes were identified with protein-protein interaction (PPI) network, including PTPRC, TGFB1, EGF, MYC, ITGB2, CTSS, FN1, CCL5, KNG1, and CD86. Additionally, sub-networks analyse was also performed by using MCODE plugin. In conclusion, the novel DEGs and pathways in ccRCC identified in this study may provide new insight into the underlying molecular mechanisms that facilitates RCC carcinogenesis.

808nm light triggered black TiO2 nanoparticles for killing of bladder cancer cells.

The black TiO2 nanoparticles are synthesized via a facile calcination method combined with an in-situ controllable solid-state reaction approach. The results indicate that the photocatalyst with a narrow band gap of ~2.32 eV extends the photoresponse to visible light and near infrared region. And thus more reactive oxygen species can be obtained to induce the cell-killing under 808 nm light triggering. The as-obtained black TiO2 nanoparticles exhibiting low toxicity, good biocompatibility and high anticancer effect in vitro, is demonstrated as efficient photosensitizers for phototherapy to kill the bladder cancer cells. These findings suggest that the facile synthetic black TiO2 nanomaterials will have broad application in biomedicine.

Downregulation of lncRNA SDPR-AS is associated with poor prognosis in renal cell carcinoma.

Renal cell carcinoma (RCC) is a common type of kidney cancer. Normally, surgical treatment can prolong life, but only for patients with early stage tumors. However, it is difficult for early detection strategies to distinguish between benign and malignant kidney tumors. Therefore, potential biomarkers for early diagnosis and prognosis of RCC are needed. Intriguingly, mounting evidence has demonstrated that many long noncoding RNAs (lncRNAs) are strongly linked to cancers. Indeed, promising RCC-associated lncRNA biomarkers have also been identified. However, the functional and prognostic roles of the antisense (AS) serum deprivation response (SDPR) lncRNA (SDPR-AS) in RCC remain largely unknown. The aims of this study were to investigate the expression and prognostic relevance of SDPR-AS in RCC. We uncovered the downregulated expressions of both lncRNA SDPR-AS and its protein-coding gene, SDPR, in RCC tissues compared to the matched normal tissues. Furthermore, SDPR-AS and SDPR expressions were positively correlated. Overexpression and knockdown experiments suggested that SDPR-AS and SDPR were coregulated in RCC cell lines. In addition, overexpression of SDPR-AS suppressed cell migration and invasion, but not cell growth. Furthermore, expression of SDPR-AS was associated with tumor differentiation and lymphatic metastasis. Kaplan-Meier survival and log-rank tests demonstrated the association of elevated expression of SDPR-AS with increased overall survival. In conclusion, our results suggest that the SDPR-AS may serve as a prognostic biomarker and therapeutic target of RCC.

Vascular endothelial growth factor gene polymorphisms and the risk of renal cell carcinoma: Evidence from eight case-control studies.

BACKGROUND: Vascular endothelial growth factor (VEGF) protein plays important role in renal cell carcinoma (RCC) development and progression. VEGF gene polymorphisms can alter the protein concentrations and might be associated with renal cell carcinoma risk. However, the results of studies investigating the association between VEGF polymorphisms and renal cell carcinoma risk are inconsistent. Thus, a meta-analysis was performed. METHODS: We selected eligible studies via electronic searches. Only high-quality studies were included based on specific inclusion criteria and the Newcastle-Ottawa Scale (NOS). RESULTS: Eight studies primarily focusing on seven polymorphisms were included in our meta-analysis. Our results showed dramatically high risks for renal cell carcinoma were found regarding most genetic models and alleles of the +936C/T polymorphism (except CT vs. CC). In addition, significant increased renal cell carcinoma risks were found regarding all genetic models and alleles of the -2578C/A polymorphism. However, no significant associations were found between renal cell carcinoma risk and the +1612G/A, -460T/C, -634G/C, -405G/C or -1154G/A polymorphisms. CONCLUSIONS: Our meta-analysis indicates that the +936C/T and -2578C/A polymorphisms of VEGF are associated with an increased risk for renal cell carcinoma. Additional rigorous analytical studies are needed to confirm our results.

Programmed Cell Death-1 Polymorphisms Decrease the Cancer Risk: A Meta-Analysis Involving Twelve Case-Control Studies.

Programmed cell death-1 (PD-1) plays an important inhibitory role in anti-tumor responses, so it is considered as a powerful candidate gene for individual's genetic susceptibility to cancer. Recently, some epidemiological studies have evaluated the association between PD-1 polymorphisms and cancer risk. However, the results of the studies are conflicting. Therefore, a meta-analysis was performed. We identified all studies reporting the relationship between PD-1 polymorphisms and cancers by electronically searches. According to the inclusion criteria and the quality assessment of Newcastle-Ottawa Scale (NOS), only high quality studies were included. A total of twelve relevant studies involving 5,206 cases and 5,174 controls were recruited. For PD-1.5 (rs2227981) polymorphism, significantly decreased cancer risks were obtained among overall population, Asians subgroup and population-based subgroup both in TT vs. CC and TT vs. CT+CC genetic models. In addition, a similar result was also found in T vs. C allele for overall population. However, there were no significant associations between either PD-1.9 (rs2227982) or PD-1 rs7421861 polymorphisms and cancer risks in all genetic models and alleles. For PD-1.3 (rs11568821) polymorphism, we found different cancer susceptibilities between GA vs. GG and AA vs. AG+GG genetic models, and no associations between AA vs. GG, AA+AG vs. GG genetic models or A vs. G allele and cancer risks. In general, our results firstly indicated that PD-1.5 (rs2227981) polymorphism is associated a strongly decreased risk of cancers. Additional epidemiological studies are needed to confirm our findings.

Transurethral enucleation of the prostate versus transvesical open prostatectomy for large benign prostatic hyperplasia: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: To evaluate the efficacy and safety of transurethral enucleation of the prostate (TUEP) versus transvesical open prostatectomy (OP) for the management of large benign prostatic hyperplasia (BPH). METHODS: Randomized controlled trials (RCTs) comparing TUEP and OP were identified from PubMed, Embase and Web of Science up to February 28, 2015. A meta-analysis was conducted with the STATA 12.0 software. RESULTS: Nine RCTs including 758 patients were enrolled in our meta-analysis. There were no significant differences between the two groups in the maximum urinary flow rate at 1, 3, 6 months, 1 and 2 years: postvoiding residual urinary volume, prostate-specific antigen, international prostate symptom score and quality of life score at 1, 3, 6 months and 1 year; or international index of erectile function at 3, 6 months and 1 year. Perioperative outcomes including hemoglobin level drop, catheter period, irrigation length and hospital stay favored TUEP, while operative time and resected prostate weight favored OP. There was significantly less blood transfusion with TUEP, but no significant differences were found in other complications such as recatheterization, urinary tract infection, reintervention for clots and bleeding control, incidence of pneumonia and infarction, transient incontinence, bladder neck contracture, urethral stricture and recurrent adenoma. CONCLUSIONS: TUEP can be performed effectively and safely with functional outcomes and complications similar to OP for large BPH, whereas it has the advantages of a shorter catheter period, shorter hospital stays and less blood transfusion. These findings seem to support TUEP as the next-generation "gold standard" of surgery for large BPH.

Tamsulosin combined with solifenacin versus tamsulosin monotherapy for male lower urinary tract symptoms: a meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of tamsulosin and solifenacin combination therapy compared with tamsulosin monotherapy for male lower urinary tract symptoms (LUTS). METHODS: We identified all eligible studies that compared tamsulosin and solifenacin combination therapy with tamsulosin monotherapy for male LUTS (up to January 2015). The fixed- or random-effects model was selected depending on the proportion of heterogeneity. RESULTS: Seven articles were identified as eligible for this meta-analysis, with a total of 3063 participants. Synthetic data showed combination therapy had significant improvements in Storage International Prostate Symptom Score (WMD = -0.60; 95% CI: -0.81 to -0.38, P < 0.0001), quality of life (WMD = -0.23; 95% CI: -0.34 to -0.11, P < 0.0001), micturitions per 24 hours (WMD = -0.70; 95% CI: -0.86 to -0.55, P < 0.0001) and urgency episodes per 24 hours (WMD = -0.26; 95% CI: -0.48 to -0.05, P = 0.018). The incidence of adverse effects in the tamsulosin and solifenacin combined therapy group (30.82%) was similar to the tamsulosin monotherapy group (25.75%). Acute urinary retention was seldom reported in the studies and no clinically significant changes regarding Qmax were showed in our meta-analysis. CONCLUSIONS: Tamsulosin and solifenacin combination therapy may be a reasonable option for male LUTS patients, especially for those who have significant storage symptoms. However, PVR should be measured during treatment to assess the increase in PVR or the incidence of AUR.

MTHFR 677C>T polymorphism increases the male infertility risk: a meta-analysis involving 26 studies.

BACKGROUND AND OBJECTIVES: Methylenetetrahydrofolate reductase (MTHFR) polymorphism may be a risk factor for male infertility. However, the epidemiologic studies showed inconsistent results regarding MTHFR polymorphism and the risk of male infertility. Therefore, we performed a meta-analysis of published case-control studies to re-examine the controversy. METHODS: Electronic searches of PubMed, EMBASE, Google Scholar and China National Knowledge Infrastructure (CNKI) were conducted to select eligible literatures for this meta-analysis (updated to June 19, 2014). According to our inclusion criteria and the Newcastle-Ottawa Scale (NOS), only high quality studies that observed the association between MTHFR polymorphism and male infertility risk were included. Crude odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of association between the MTHFR polymorphism and male infertility risk. RESULTS: Twenty-six studies involving 5,575 cases and 5,447 controls were recruited. Overall, MTHFR 677C>T polymorphism showed significant associations with male infertility risk in both fixed effects (CT+TT vs. CC: OR = 1.34, 95% CI: 1.23-1.46) and random effects models (CT+TT vs. CC: OR = 1.39, 95% CI: 1.19-1.62). Further, when stratified by ethnicity, sperm concentration and control sources, the similar results were observed in Asians, Caucasians, Azoo or OAT subgroup and both in population-based and hospital-based controls. Nevertheless, no significant association was only observed in oligo subgroup. CONCLUSIONS: Our results indicated that the MTHFR polymorphism is associated with an increased risk of male infertility. Further well-designed analytical studies are necessary to confirm our conclusions and evaluate gene-environment interactions with male infertility risk.

USP28 is a potential prognostic marker for bladder cancer.

This study was conducted to analyze the expression of the ubiquitin-specific protease Usp28 and assess its clinical significance in human bladder cancer. mRNA and protein expression levels of Usp28 were determined by real-time polymerase chain reaction (PCR) and Western blot in 24 paired bladder cancers and the adjacent non-cancerous tissues. In addition, the expression of Usp28 protein in 186 bladder cancers was also determined by immunohistochemistry. The relationship between expression of Usp28 and clinico-pathologic features and prognosis was finally evaluated. Usp28 was expressed at a higher level in bladder cancers compared to adjacent non-cancerous tissues at both the mRNA and protein levels in 24 paired samples (all P < 0.01). In immunohistochemical examination, 78 (41.9%) of 186 cases displayed low Usp28 expression in cancerous tissues, whereas 108 (58.1%) cases displayed high Usp28 expression. In the universal analysis, Usp28 correlated strongly with histopathological grade, clinical stage, tumor number and recurrence rate (P = 0.0001, 0.0001, 0.0001 and 0.0051, respectively), but did not correlate with gender or age (P = 0.5588 and 0.6574). After multiple analysis of the above factors and consideration of confounding factors, tumor number, histological grade, clinical stage, and recurrence were related to Usp28 expression (P = 0.001, 0.001, 0.001 and 0.001, respectively). Finally, Usp28 expression was indentified as a independent predictors of survival (P = 0.001). Usp28 protein expression is potentially valuable in prognostic evaluation of bladder cancer.

Galectin-3 inhibition sensitizes human renal cell carcinoma cells to arsenic trioxide treatment.

The anti-tumor effects of arsenic trioxide (ATO) were well established in acute promyelocytic leukemia, but not in renal cell carcinoma (RCC). Recent evidences indicate that galectin-3 (Gal-3) plays an anti-apoptotic role in chemotherapy induced tumor cell death. This study was intended to clarify the exact roles of Gal-3 performed in ATO-induced apoptosis in RCC cells. Weak apoptosis was observed in Gal-3-positive RCC cells (Caki-1, Caki-2, 786-0, and ACHN) following ATO treatment. However, ATO treatment upregulated Gal-3 expression concurrently caused a Synexin-cooperated translocation of Gal-3 from the nucleus to the cytoplasm. Gal-3-knockdown cells were more sensitive to ATO treatment as indicated by a strong mitochondria-dependent apoptosis following ATO treatment. Meanwhile, Gal-3 was found to inhibit ATO-induced apoptosis through enhancing Bcl-2 expression and stabilizing mitochondria. To confirm the results obtained from genetic method, we employed a Gal-3 inhibitor, modified citrus prectin (MCP), and co-treated the RCC cells with ATO. The cells showed an increased apoptosis in the syngeneic application of Gal-3 inhibition and ATO compared with ATO application alone. Based on these results, we conclude that Gal-3 inhibition sensitizes human renal cell carcinoma cells to ATO treatment through increasing mitochondria-dependent apoptosis. Our studies implicate synergetic application of ATO and Gal-3 inhibition as a potential strategy for RCC treatment.

Expression of Opa interacting protein 5 (OIP5) is associated with tumor stage and prognosis of clear cell renal cell carcinoma.

Opa interacting protein 5 (OIP5), overexpressed in some types of human cancers, has been reported to be associated with the carcinogenesis of human cancer. However, the biological function and clinical significance of OIP5 in human Clear Cell Renal Cell Carcinoma (CCRCC) remains unknown. In the present study, we found the expression of OIP5 was markedly upregulated in surgical CCRCC specimens and CCRCC cell lines. Immunohistochemical analysis revealed that paraffin-embedded archival CCRCC specimens exhibited higher levels of OIP5 expression than normal renal tissues. Further statistical analysis suggested the upregulation of OIP5 was positively correlated with the Fuhrman grade (P = 0.02), T classification (P = 0.015), N classification (P = 0.018) and clinical stage (P = 0.035). Also, patients with high OIP5 expression dramatically exhibited shorter survival time (P = 0.001). In addition, the OIP5 expression was an independent prognostic marker of overall survival of CCRCC patients in a multivariate analysis (P = 0.008). Experimentally, we demonstrated that silencing OIP5 in CCRCC cell lines by specific siRNA clearly inhibited cell growth. In conclusion, our findings suggested that OIP5 could be a valuable marker of CCRCC progression and prognosis, and a promising therapeutic target for CCRCC.

Genetic polymorphisms of GSTM1, GSTT1, and GSTP1 with prostate cancer risk: a meta-analysis of 57 studies.

BACKGROUND AND OBJECTIVES: The GSTM1, GSTT1 and GSTP1 polymorphisms might be involved in inactivation of procarcinogens that contribute to the genesis and progression of cancers. However, studies investigating the association between GSTM1, GSTT1 or GSTP1 polymorphisms and prostate cancer (PCa) risk report conflicting results, therefore, we conducted a meta-analysis to re-examine the controversy. METHODS: Published literature from PubMed, Embase, Google Scholar and China National Knowledge Infrastructure (CNKI) were searched (updated to June 2, 2012). According to our inclusion criteria, studies that observed the association between GSTM1, GSTT1 or GSTP1 polymorphisms and PCa risk were included. The principal outcome measure was the odds ratio (OR) with 95% confidence interval (CI) for the risk of PCa associated with GSTM1, GSTT1 and GSTP1 polymorphisms. RESULTS: Fifty-seven studies involving 11313 cases and 12934 controls were recruited. The overall OR, which was 1.2854 (95% CI = 1.1405-1.4487), revealed a significant risk of PCa and GSTM1 null genotype, and the similar results were observed when stratified by ethnicity and control source. Further, the more important is that the present study first reported the high risks of PCa for people who with dual null genotype of GSTM1 and GSTT1 (OR = 1.4353, 95% CI = 1.0345-1.9913), or who with GSTT1 null genotype and GSTP1 A131G polymorphism (OR = 1.7335, 95% CI = 1.1067-2.7152). But no association was determined between GSTT1 null genotype (OR = 1.102, 95% CI = 0.9596-1.2655) or GSTP1 A131G polymorphism (OR = 1.0845, 95% CI = 0.96-1.2251) and the PCa risk. CONCLUSIONS: Our meta-analysis suggested that the people with GSTM1 null genotype, with dual null genotype of GSTM1 and GSTT1, or with GSTT1 null genotype and GSTP1 A131G polymorphism are associated with high risks of PCa, but no association was found between GSTT1 null genotype or GSTP1 A131G polymorphism and the risk of PCa. Further rigorous analytical studies are highly expected to confirm our conclusions and assess gene-environment interactions with PCa risk.

Glutathione S-transferase T1 polymorphism contributes to bladder cancer risk: a meta-analysis involving 50 studies.

Glutathione S-transferase T1 (GSTT1) is implicated in the inactivation of procarcinogens that contribute to cancer progression. However, studies investigating the association between GSTT1 polymorphism and bladder cancer (BC) risk have reported conflicting results; therefore, a meta-analysis was conducted. Fifty studies with 10,805 cases and 13,332 controls were recruited. The overall odds ratio for the GSTT1 null genotype was 1.1502 (95% CI=1.0384-1.2741). When stratified by ethnicity, significantly increased risk was only found for Caucasians. In Asians subgroup, interestingly, decreased BC risks were found in the Korean and Japanese populations but not in the Chinese population. When stratified by control sources, a slightly elevated risk was found in population-based but not in hospital-based studies. Besides, smoking was not found to modify the association between the GSTT1 null genotype and BC risk. When combined with the GSTM1 null genotype, a remarkably increased risk was found for BC. In general, our results suggest that the GSTT1 null genotype is associated with an increased risk of BC. Smoking did not modify the association between the GSTT1 null genotype and BC risk. Furthermore, a strong association was observed between the combination of GSTT1 null and GSTM1 null genotype and risk of BC. Further epidemiological studies will be needed to confirm our findings.