Noninvasive assessment of significant liver fibrosis in rabbits by spectral CT parameters and texture analysis.

PURPOSE: Noninvasive assessment of significant liver fibrosis in rabbits by spectral CT parameters and texture analysis. MATERIALS AND METHODS: Thirty-three rabbits were randomly divided into 27 carbon tetrachloride-induced liver fibrosis group and 6 control group. Spectral CT contrast-enhanced scan was performed in batches, and the liver fibrosis was staged according to the histopathological results. The portal venous phase spectral CT parameters [70 keV CT value, normalized iodine concentration (NIC), spectral HU curve slope (λHU)] were measured, and MaZda texture analysis was performed on 70 keV monochrome images. Three dimensionality reduction methods and four statistical methods in B11 module were used to perform discriminant analysis and calculate misclassified rate (MCR), and ten texture features under the lowest combination of MCR were statistically analyzed. Receiver operating characteristic curve (ROC) was used to calculate the diagnostic performance of spectral parameters and texture features for significant liver fibrosis. Finally, the binary logistic regression was used to further screen independent predictors and establish model. RESULTS: A total of 23 experimental rabbits and 6 control rabbits were included, of which 16 had significant liver fibrosis. Three spectral CT parameters with significant liver fibrosis were significantly lower than those of non-significant liver fibrosis (p < 0.05), and the AUC ranged from 0.846 to 0.913. The combination analysis of mutual information (MI) and nonlinear discriminant analysis (NDA) had the lowest MCR, which with 0%. In the filtered texture features, four were statistically significant and AUC > 0.5, ranges from 0.764 to 0.875. The logistic regression model showed that Perc.90% and NIC could be used as independent predictors, the overall prediction accuracy of the model was 89.7% and the AUC was 0.976. CONCLUSION: Spectral CT parameters and texture features have high diagnostic value for predicting significant liver fibrosis in rabbits, and the combination of the two can improve its diagnostic efficiency.

Diagnostic Accuracy of Transient Elastography and Two-Dimensional Shear Wave Elastography for Staging Liver Fibrosis in Children or Adolescents: A Systematic Review and Meta-Analysis.

BACKGROUND: Few studies comprehensively compared the performance of transient elastography (TE) and two-dimensional shear wave elastography(2D-SWE) to diagnose the stage of liver fibrosis in children and adolescents. We assessed the diagnostic performance of these non-invasive imaging techniques from published studies. METHODS: To evaluate the diagnostic performance of TE and 2D-SWE, we searched the PubMed, Embase, Web of Science, and Cochrane Library databases until November 13, 2021, for studies that diagnosed liver fibrosis in children and adolescents. Pooled sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratios, and area under the receiver operating characteristic curve were estimated using the bivariate model. We also performed a subgroup analysis of various research characteristics. RESULTS: Twenty-seven studies with 1956 patients were included in the analysis. The sensitivity and specificity of TE and 2D-SWE for detecting liver fibrosis in all stages were greater than 0.82. For the detection of significant fibrosis, advanced fibrosis and cirrhosis, the summary AUC was 0.90 (95% CI: 0.87-0.92), 0.95 (95% CI: 0.93-0.96) and 0.95 (95% CI: 0.93-0.97) for TE, and the summary AUC was 0.92 (95% CI: 0.89-0.94), 0.94 (95% CI: 0.92-0.96) and 0.96 (95% CI: 0.94-0.97) for 2D-SWE, respectively. Both imaging methods detected significant heterogeneity. CONCLUSION: TE and 2D-SWE can provide accurate non-invasive staging of liver fibrosis in children or adolescents and are a promising technology, particularly for advanced liver fibrosis and cirrhosis, with a high potential to replace liver biopsy.

Diagnostic performance of radiomics in predicting axillary lymph node metastasis in breast cancer: A systematic review and meta-analysis.

Background: This study aimed to perform a meta-analysis to evaluate the diagnostic performance of radiomics in predicting axillary lymph node metastasis (ALNM) and sentinel lymph node metastasis (SLNM) in breast cancer. Materials and methods: Multiple electronic databases were systematically searched to identify relevant studies published before April 29, 2022: PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Data. The quality of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. The overall diagnostic odds ratio (DOR), sensitivity, specificity, and area under the curve (AUC) were calculated to evaluate the diagnostic performance of radiomic features for lymph node metastasis (LNM) in patients with breast cancer. Spearman's correlation coefficient was determined to assess the threshold effect, and meta-regression and subgroup analyses were performed to explore the possible causes of heterogeneity. Results: A total of 30 studies with 5611 patients were included in the meta-analysis. Pooled estimates suggesting overall diagnostic accuracy of radiomics in detecting LNM were determined: DOR, 23 (95% CI, 16-33); sensitivity, 0.86 (95% CI, 0.82-0.88); specificity, 0.79 (95% CI, 0.73-0.84); and AUC, 0.90 (95% CI, 0.87-0.92). The meta-analysis showed significant heterogeneity between sensitivity and specificity across the included studies, with no evidence for a threshold effect. Meta-regression and subgroup analyses showed that combined clinical factors, modeling method, region, and imaging modality (magnetic resonance imaging [MRI], ultrasound, computed tomography [CT], and X-ray mammography [MMG]) contributed to the heterogeneity in the sensitivity analysis (P < 0.05). Furthermore, modeling methods, MRI, and MMG contributed to the heterogeneity in the specificity analysis (P < 0.05). Conclusion: Our results show that radiomics has good diagnostic performance in predicting ALNM and SLNM in breast cancer. Thus, we propose this approach as a clinical method for the preoperative identification of LNM.

COMMD3 Expression Affects Angiogenesis through the HIF1α/VEGF/NF-κB Signaling Pathway in Hepatocellular Carcinoma In Vitro and In Vivo.

Background: High expression of copper metabolizing MURR1 domain (COMMD3) is significantly correlated with poor prognosis in hepatocellular carcinoma (HCC) patients. Here, we explored the mechanism by which COMMD3 affects HCC angiogenesis through the HIF1α/VEGF/NF-κB signaling pathway. Methods: SK-Hep1 and Hep-3B cell lines were transfected by COMMD3 overexpression and RNA interference lentivirus and verified using RT-qPCR and western blotting techniques. Using RNA sequencing, we analyzed differentially expressed genes in COMMD3-overexpressed and COMMD3-knockdown HCC cells. Altogether, colony formation assay, wound healing assay, transwell cell invasion assay, flow cytometry apoptosis experiments, HUVEC tube formation detection, phalloidin staining assay, western blotting, immunohistochemical staining, and a nude mouse xenograft model were used for experimental verification. Results: Lentivirus COMMD3 overexpression and knockdown were successfully established in HCC cells. COMMD3 overexpression significantly promoted the proliferation, angiogenesis, migration, and invasion capacities of HCC cells with no obvious effect on apoptosis versus controls while COMMD3 knockdown showed the opposite trend. The expression and protein levels of COMMD3 as well as HIF1α, VEGF, and NF-κB were increased in COMMD3-overexpressing HCC cells versus control cells, while they were reduced after COMMD3 knockdown. In addition, RNA-seq indicated that COMMD3 is an indispensable gene for HCC angiogenesis through HIF1α and NF-κB signaling pathways. Conclusion: This study showed that low expression of COMMD3 can inhibit HCC angiogenesis by suppressing the HIF1α/VEGF/NF-κB pathway. This implicates COMMD3 as a potential biomarker for improving the therapeutic outcome of HCC.

Investigating the Association between COMMD3 Expression and the Prognosis of Hepatocellular Carcinoma.

The Copper Metabolism MURR1 Domain (COMMD) family proteins are known to play roles in promoting or inhibiting the proliferation, migration and invasion of tumor cells. However, the role of COMMD3 in hepatocellular carcinoma are still unclear. By investigating the TCGA datasets, we found that the mRNA expression of COMMD3 was significantly upregulated in hepatocellular carcinoma tissue compared with normal liver tissue, which was further supported by Oncomine dataset, Western blot, qRT-PCR, and IHC analysis. Moreover, Kaplan-Meier survival analysis showed that the high expression of COMMD3 was associated with poor overall survival (OS) and disease-free survival (DFS). Consistently, the clinic-pathological analysis found that the overexpression of COMMD3 was correlated with advanced TNM stage, advanced T stage and vascular invasion. By performing multivariate analysis, we found that the expression of COMMD3 was an independent influencing factor on OS and DFS. Furthermore, we knocked down COMMD3 in HCC cells via RNA interference. The results showed that silencing COMMD3 could inhibit the migration, invasion, and angiogenesis of HCC cells. Finally, we established xenograft tumor model in nude mice, and the knockdown of COMMD3 suppressed tumor growth and angiogenesis. In summary, our study showed that the high expression of COMMD3 was correlated with poor prognosis in HCC patients and contributed to migration, invasion and angiogenesis of HCC cells.

HIF-1α RNAi Combined with Asparagus Polysaccharide Exerts an Antiangiogenesis Effect on Hepatocellular Carcinoma In Vitro and In Vivo.

BACKGROUND: Hepatocellular carcinoma (HCC) is the main form of primary liver cancer and is one of the most prevalent and life-threatening malignancies globally. Hypoxia activates hypoxia-inducible factor-1α (HIF-1α), which is the key factor in promoting angiogenesis in HCC. Currently, there are few studies on the effects of HIF-1α-targeted gene therapy combined with traditional Chinese herbal extracts. OBJECTIVE: We investigated the effects of HIF-1α RNA interference (RNAi) combined with asparagus polysaccharide (ASP) on HCC in vitro and in vivo. METHODS: CCK-8, wound-healing, transwell, and human umbilical vein endothelial cell tube formation assays were performed to evaluate the proliferation, migration, invasion, and angiogenesis of HCC cells in vitro. In addition, western blotting, qPCR, and immunohistochemistry were performed to detect the expression of HIF-1α, vascular endothelial growth factor, AKT, p-AKT, ERK, p-ERK, and CD34 in HCC cells. RESULTS: The combination of HIF-1α RNAi and ASP significantly inhibited the proliferation, migration, invasion, and angiogenesis of SK-Hep1 and Hep-3B cells compared with the use of HIF-1α RNAi or ASP alone. In addition, this combined treatment was shown to exert these effects by regulating the PI3K and MAPK signaling pathways. These results were observed both in vitro and in vivo. CONCLUSION: Our study indicates that HIF-1α RNAi combined with ASP inhibits angiogenesis in HCC via the PI3K and MAPK signaling pathways. Thus, we suggest that this combination may be an effective method for the comprehensive treatment of HCC, which may provide new ideas for the treatment of other malignant tumors.

Asparagus Polysaccharide inhibits the Hypoxia-induced migration, invasion and angiogenesis of Hepatocellular Carcinoma Cells partly through regulating HIF1α/VEGF expression via MAPK and PI3K signaling pathway.

Aim: Although there are so many treatment strategies used for hepatocellular carcinoma (HCC), the overall survival (OS) of HCC patients still remains very low. In our previous studies, asparagus polysaccharide (ASP) has been demonstrated to suppress proliferation, migration, invasion and angiogenesis of HCC cells under normoxic conditions in vitro. However, the inhibitory effects of ASP on the hypoxia-induced migration, invasion and angiogenesis of HCC cells still remain largely unexplored. Materials and methods: Cell Counting Kit-8 (CCK-8) assay, transwell assay, and tube formation assay were used to determine the effects of ASP on hypoxia-induced proliferation, migration, invasion and angiogenesis of HCC cells. ELISA, Western blotting analysis and immunofluorescence assay were used to confirm the effects of ASP on the expressions of HIF-1α and VEGF at the protein level. Moreover, effects of ASP on signaling pathway-related proteins were investigated by Western blotting analysis. Immunohistochemistry (IHC) assay was applied to test the effects of ASP on angiogenesis-associated proteins of tumor cells. Results: We showed that ASP effectively suppressed hypoxia-induced proliferation, migration, invasion and angiogenesis of SK-Hep1 and Hep-3B cells in a dose-dependent manner. In addition, the inhibitory effect of ASP might be partly attributed to down-regulation of HIF1α and VEGF proteins in SK-Hep1 and Hep-3B cells under hypoxic conditions. Moreover, signaling pathway study indicated that ASP significantly down-regulated the hypoxia-induced expressions of p-AKT, p-mTOR and p-ERK, while it had little effects on AKT, mTOR and ERK. Besides, SK-Hep1 xenograft tumor models in nude mice further confirmed that the inhibitory effect of ASP on xenograft tumors might be exerted partly via down-regulation of HIF1α and VEGF through blocking MAPK and PI3K signaling pathways. Conclusions: Our findings suggested that ASP suppressed the hypoxia-induced migration, invasion and angiogenesis of HCC cells partly through regulating HIF-1α/VEGF expression via MAPK and PI3K signaling pathways.

Diagnostic rather than prognostic markers-relationship between EpCAM overexpression and lung cancer: a meta-analysis.

BACKGROUND: Epithelial cell adhesion molecule (EpCAM) is one of the most commonly used markers of cancer stem cells (CSCs). However, the diagnostic and prognostic significance of EpCAM in lung cancer remains largely undetermined. In the present study, we systematically summarized and elucidated the correlation between EpCAM overexpression and lung cancer through a meta-analysis. METHODS: Six databases (PubMed, Web of Science, Cochrane Library, and Embase, CnKI and Wanfang Database) were systematically searched. Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) criteria were adopted to assess the qualities of the included studies. Relevant data were extracted for meta-analysis using the Stata12.0 software. Unadjusted mixed odds ratios (ORs) or hazard ratios (HRs) with 95% confidence interval (95% CI) were estimated to evaluate the correlation between EpCAM overexpression and lung cancer. The sensitivity and specificity of the included studies were used to construct the summary receiver operator characteristic (SROC) curve and calculate the area under the SROC curve (AUC). RESULTS: A total of 14 studies consisting of 2,658 lung cancer patients were included following the PICOS principle. We found that the EpCAM expression was significantly higher in lung cancer patients compared with normal controls, including patients with benign pulmonary diseases (OR =63.71, 95% CI, 14.59-278.21, P=0.003) and healthy individuals (OR =520.08, 95% CI, 16.38-16,510.80, P=0.002), and its overexpression was negatively associated with the TNM stage (III + IV) (OR =0.41, 95% CI, 0.21-0.82, P=0.073. The combined sensitivity and specificity of EpCAM overexpression in the diagnosis of lung cancer were 0.79 (95% CI, 0.59-0.90) and 0.98 (95% CI, 0.95-0.99), respectively, and the SROC-AUC was 0.98 (95% CI, 0.97-0.99). Multivariate analysis of 322 lung cancer patients showed that there was no significant correlation between the EpCAM overexpression and prognosis of lung cancer (HR =2.28, 95% CI, 0.80-6.51, P=0.002). Deeks' funnel plot analysis showed the existence of publication bias (P=0.000). CONCLUSIONS: Our present findings suggested that EpCAM overexpression was not sensitive enough to predict the prognosis of lung cancer. Moreover, it was also a potential diagnostic indicator for lung cancer and correlated with TNM staging of lung cancer.

Hierarchical marketing mix models with sign constraints.

Marketing mix models (MMMs) are statistical models for measuring the effectiveness of various marketing activities such as promotion, media advertisement, etc. In this research, we propose a comprehensive marketing mix model that captures the hierarchical structure and the carryover, shape and scale effects of certain marketing activities, as well as sign restrictions on certain coefficients that are consistent with common business sense. In contrast to commonly adopted approaches in practice, which estimate parameters in a multi-stage process, the proposed approach estimates all the unknown parameters simultaneously using a constrained maximum likelihood approach and a Hamiltonian Monte Carlo algorithm. We present results on real datasets to illustrate the use of the proposed solution algorithms.

Upregulation of hypoxia-inducible factor 1α mRNA expression was associated with poor prognosis in patients with hepatocellular carcinoma.

BACKGROUND: HIF1α mRNA expression in hepatocellular carcinoma (HCC) tissues and its relationship with the prognosis in HCC patients is still unclear. We performed this study to investigate the expression of HIF1α mRNA and its correlation with the prognosis in HCC patients. MATERIALS AND METHODS: GSE14520 and Oncomine database were used to analyse the differential expression of HIF1α mRNA among HCC tissues and corresponding peritumour tissues or normal liver tissues. The relationship between HIF1α mRNA expression and the clinicopathological features and survival in HCC patients was analysed using the GSE14520 dataset. CCK-8 assay, wound-healing assay, transwell invasion assay, tube formation assay, and subcutaneous xenograft tumour assays using nude mice were used to confirm the function of HIF1α. RESULTS: Expression of HIF1α mRNA was significantly upregulated in HCC tissues (P<0.05 in all cases); this was supported by the results of the Western blotting (P=0.031) and IHC analyses. Our analysis of the clinicopathological features of HCC patients indicated that high HIF1α mRNA expression was strongly related with TNM stage III (P=0.002) and BCLC stage C (P=0.038). Survival analysis demonstrated that HCC patients with high HIF1α mRNA expression had a short overall survival (OS) (P=0.048), but showed no significant difference in recurrence-free survival (RFS) (P=0.066) compared to patients with low HIF1α mRNA expression. We further demonstrated that HIF1α promoted the proliferation, migration, invasion, and angiogenic ability of HCC cells, by using the stably transformed SK-Hep1 and Hep-3B cell lines showing HIF1α overexpression. Finally, xenograft tumour models of nude mice showed that RNA interference-mediated HIF1α silencing suppressed tumour growth and angiogenesis in HCC. CONCLUSION: Our study suggests that the upregulation of HIF1α mRNA, which is found in HCC tissues and associated with poor prognosis in HCC patients, contributed to the proliferation, migration, invasion, and angiogenic ability of HCC cells.

Asparagus Polysaccharide Suppresses the Migration, Invasion, and Angiogenesis of Hepatocellular Carcinoma Cells Partly by Targeting the HIF-1α/VEGF Signalling Pathway In Vitro.

Hypoxia-inducible factor-1α (HIF-1α) plays a key role by triggering the transcriptional activation of a number of genes involved in migration, invasion, and angiogenesis in hepatocellular carcinoma (HCC). Thus, suppressing tumour growth by targeting the HIF-1α/VEGF signalling pathway represents a promising strategy for the treatment of HCC. In our previous studies, we found that asparagus polysaccharide (ASP) suppressed the proliferation and promoted the apoptosis of HCC cells both in vivo and in vitro. To further explore the potential mechanisms of the antitumor effects of ASP in HCC, we investigated effects of ASP on the migration, invasion, and angiogenesis of HCC cells (SK-Hep1 and Hep-3B) using an in vitro experimental model. First, we found that ASP effectively suppressed the proliferation of the SK-Hep1 and Hep-3B cells but did not cause significant cytotoxicity in normal liver cells (L-O2). Then, we found that ASP inhibited the migration and invasion of the SK-Hep1 and Hep-3B cells and HCC cells-induced angiogenesis of human umbilical vein endothelial cells in a concentration-dependent manner. Mechanistic studies revealed that the inhibition of migration, invasion, and angiogenesis by ASP in the SK-Hep1 and Hep-3B cells might occur via the downregulation of HIF-1α/VEGF signalling pathway. Finally, our results also showed that the inhibition of HIF-1α by ASP may be mediated through the downregulation of the phosphorylation levels of AKT, mTOR, and ERK. In conclusion, our results suggest that ASP suppresses the migration, invasion, and angiogenesis of HCC cells partly via inhibiting the HIF-1α/VEGF signalling pathway.

FABP5 regulates the proliferation of clear cell renal cell carcinoma cells via the PI3K/AKT signaling pathway.

Clear cell renal cell carcinoma (ccRCC) has been associated with one of the highest mortality rates among all cancers. Fatty acid binding proteins (FABPs) are 14­15 kDa proteins that are highly abundant in the cytosol of most tissues. FABP5, a member of the FABP family, has been observed to promote tumor cell growth in numerous cancer types. In order to investigate the function of FABP5 in ccRCC cells in the present study, RNA sequencing data from The Cancer Genome Atlas were analyzed to determine the expression levels of FABP5 in ccRCC patient samples. Survival and Cox regression analyses were performed to measure the association between FABP5 expression and clinicopathological features of patients with ccRCC. Subsequent in vitro experiments downregulated or overexpressed FABP5 in Caki­1 and 786O ccRCC cells using lentiviral vectors to evaluate cell proliferation ability, and a xenograft transplantation model was established to examine the effect of FABP5 on tumorigenesis in vivo. The results demonstrated that FABP5 expression was significantly upregulated in samples from patients with ccRCC when compared with normal tissue samples. High FABP5 expression was also significantly correlated with tumor and metastasis classifications and predicted poor survival in patients with ccRCC. In ccRCC cells, silencing of FABP5 significantly inhibited cell proliferation, while overexpression of FABP5 promoted cell proliferation when compared to the respective controls. In addition, treatment with the phosphatidylinositol­4,5­bisphosphate 3­kinase (PI3K)/AKT inhibitor, LY294002, attenuated the pro­proliferative effects of exogenous FABP5 expression in Caki­1 and 786O cells. This indicated that the PI3K/AKT signaling pathway may be partially involved in the FABP5­mediated increase in ccRCC cell proliferation. Furthermore, FABP5 was observed to regulate tumor growth in nude mice in vivo. In conclusion, the results of the present study suggest that FABP5 may exert a pro­proliferative role in ccRCC and may be associated with malignant progression and tumorigenesis.

Lymph node dissection could bring survival benefits to patients diagnosed with clinically node-negative upper urinary tract urothelial cancer: a population-based, propensity score-matched study.

OBJECTIVES: To evaluate the survival benefits that lymph node dissection (LND) brought to clinically node-negative upper tract urothelial carcinoma (UTUC) patients. METHODS: Non-metastatic node-negative UTUC patients were identified from the Surveillance, Epidemiology and End Results database. N0 patients were naturally divided as cN0-pNx group (clinically diagnosed as N0 without LND performed) and cNx-pN0 group (pathologically diagnosed as node-negative no matter what clinical node status they have). RESULTS: Of the 2731 patients included, 2240 and 491 cases were cN0-pNx and cNx-pN0, respectively. The overall survival (OS) of cNx-pN0 patients was significantly better than that of cNx-pN0 patients (p = 0.022). After propensity score matching, the survival of cNx-pN0 patients was still significantly better than cN0-pNx group. Besides, multivariate analyses showed cNx-pN0 (received LND) was an independent favorable prognostic factor for OS and CSS compared with cN0-pNx (no LND). Survival advantages of pN0 group were more significant in ≥ T2 patients and patients with tumor size ≤ 5 cm. Even in N0 patients who received adjuvant treatment, LND still brought obvious survival improvement (HRos = 0.565, p = 0.013; HRcss = 0.607, p = 0.046). CONCLUSION: LND could improve survival outcomes in patients with clinically node-negative UTUC, especially for those with muscle-invasive diseases (T2-4 stages) or smaller tumor size (≤ 5 cm). Adjuvant treatment after nephroureterectomy is incapable of replacing the therapeutic role of LND.

Pathologically examining a minimum of three lymph nodes could better determine node negativity in patients with non-metastatic chromophobe renal cell carcinoma.

OBJECTIVE: To evaluate the prognostic value of lymph node (LN) involvement for patients with chromophobe renal cell carcinoma (chRCC) and ascertain the minimum number of LNs that need to be pathologically examined to reliably diagnose a patient with node negative chRCC. METHODS: From 2004 to 2014, non-metastatic chRCC patients receiving radical nephrectomy together with lymphadenectomy were identified from the Surveillance, Epidemiology and End Results (SEER) database. The primary outcome was overall survival (OS). RESULTS: Two hundred and forty-six patients received lymph node dissection during the surgery. Of the patients, 24 (10%) had pathologically confirmed positive LN. Multivariate Cox regression model showed that positive LN was an independent unfavorable predictor for OS (HR = 2.83, 95%CI = 1.14-6.98, P = 0.024). More importantly, LN(-) patients with at least three LNs dissected had significantly better OS compared with when 1-2 LNs were examined (P = 0.048). Multivariate analysis confirmed that in LN(-) patients, the examination of three or more LNs could independently predict better OS compared with patients with only 1-2 LNs dissected (HR≥3LNs = 0.362, 95% CI = 0.135-0.972, P = 0.044). Additionally, the likelihood of finding at least one positive LN was significantly higher on dissection of ≥3 LNs compared with examination of 1-2 LNs (15% vs 5%, P = 0.018). Decision curve analysis found a better clinical validity of the '3 LNs examined'-based classification compared with the traditional LN(-)/LN(+) classification. CONCLUSION: The proportion of positive LNs in chRCC was far from neglectable and LN metastasis could independently predict unfavorable OS. We recommended a minimum of three LNs should be pathologically examined in order to reliably determine node negative.

Nomograms to Predict Individual Prognosis of Patients with Primary Small Cell Carcinoma of the Bladder.

Objectives: To develop reliable nomograms to estimate individualized overall survival (OS) and cancer specific survival (CSS) for patients with primary small cell carcinoma of the bladder (SCCB) and compare the predictive value with the AJCC stages. Patients and Methods: 582 eligible SCCB patients identified in the Surveillance, Epidemiology, and End Results (SEER) dataset were randomly divided into training (n=482) and validation (n=100) cohorts. Akaike information criterion was used to select the clinically important variables in multivariate Cox models when establishing nomograms. The performance of nomograms was bootstrapped validated internally and externally using the concordance index (C-index) with 95% confidence interval (95% CI) and calibration curves and was compared with that of the AJCC stages using C-index, Kaplan-Meier curves and decision curve analysis (DCA). Results: Two nomograms shared common indicators including age, tumor size, T stage, lymph node ratio, metastases, chemotherapy, radiation and radical cystectomy, while marriage and gender were only incorporated in the OS nomogram. The C-indices of nomograms for OS and CSS were 0.736 (95%CI 0.711-0.761) and 0.731(95%CI 0.704-0.758), respectively, indicating considerable predictive accuracy. Calibration curves showed consistency between the nomograms and the actual observation. The results remained reproducible when nomograms were applied to the validation cohort. Additionally, comparisons between C-indices, Kaplan-Meier curves and DCA proved that the nomograms obtained obvious superiority over the AJCC stages with wide practical threshold probabilities. Conclusions: We proposed the first two nomograms for individualized prediction of OS and CSS in SCCB patients with satisfactory predictive accuracy, good robustness and wide applicability.

The Prognostic Value of Nanog Overexpression in Lung Cancer: A Meta-Analysis.

BACKGROUND: Recent several studies have showed that the nanog overexpression leads to poor prognosis in some kinds of cancer including hepatocellular carcinoma and gastrointestinal luminal cancer. However, the correlations between prognosis and clinic-pathological features and nanog overexpression in lung cancer are still not well-known. Thus, we performed a meta-analysis to evaluate the role of nanog in lung cancer. METHODS: An electronic retrieval for related studies was conducted in PubMed, Cochrane Library, Web of Science, EMBASE databases, Chinese CNKI, and the Chinese Wan Fang database up to May 2018. The relationships between nanog overexpression and overall survival (OS) and disease-free survival (DFS) as well as clinic-pathological features in lung cancer were investigated. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by STATA12. RESULTS: 11 studies containing 1422 patients were identified in our meta-analysis. The overexpression of nanog showed decreased OS (HR = 1.83, 95% CI = 1.49-2.25, P ≤ 0.001) and DFS (HR = 1.86, 95% CI = 1.2-2.9, P = 0.006). Moreover, overexpression of nanog was significantly related to differentiation (OR = 4.17, 95% CI = 2.17-6.43, P ≤ 0.001), lymph node metastasis (OR = 1.76, 95% CI = 1.06-2.91, P = 0.028) and tumor size (OR = 1.93, 95% CI = 1.17-3.20, P = 0.010), and no correlation with T stage, TNM, stage, and gender. CONCLUSIONS: Our results suggested that nanog overexpression, a hazard factor of differentiation, lymph node metastasis, and tumor size, may predicate decreased OS and DFS for lung cancer.

Prognostic value of site-specific metastases and therapeutic roles of surgery for patients with metastatic bladder cancer: a population-based study.

BACKGROUND: We aimed to evaluate the prognostic value of site-specific metastases in patients with metastatic bladder cancer and analyze the roles that surgeries play in the treatment of this malignancy. MATERIALS AND METHODS: A population-based retrospective study using Surveillance, Epidemiology and End Results dataset was performed and metastatic bladder cancer patients were classified according to the sites of metastases (bone, brain, liver, lung and distant lymph nodes). Kaplan-Meier analysis with log-rank test was used for survival comparisons. Multivariate Cox regression model was employed to analyze the effect of distant metastatic sites on overall survival (OS) and cancer-specific survival (CSS). RESULTS: A total of 1862 patients with metastatic bladder cancer from 2010 to 2014 were identified. Bone, lung and distant lymph nodes were the most common metastatic sites. Patients with bone, brain, liver and lung involvement had worse OS and CSS compared to patients without the corresponding sites of metastases. Multivariate analysis showed that bone, brain, liver and lung metastases were independent prognostic factors for both OS and CSS, while distant node metastasis was not. Moreover, patients with a single metastatic site had more favorable OS (p<0.001) and CSS (p<0.001) than patients with multisite metastases. Among single-site metastatic patients, distant nodes and liver metastases represented the best and the worst prognosis, respectively. Moreover, radical cystectomy was an independent predictor for better OS and CSS, while in patients with liver metastasis and multiple metastatic sites, RC did not bring benefits. Besides, in patients with a single metastatic site, metastasectomy seemed to be associated with favorable OS (p=0.042), especially for patients with age <65 years (p=0.006) and for muscle-invasive bladder cancer patients (p=0.031). CONCLUSION: Distant metastatic sites have differential impact on survival outcomes in patients with metastatic bladder cancer. Surgeries, including radical cystectomy and metastasectomy, might still lead to survival benefits for highly selected patients.

Preliminary study on ultrasound-guided prostate biopsy specimen scores.

Prostate cancer (PCa) is the second most frequently diagnosed cancer in males worldwide and resulted in ~258,000 cases of cancer-associated mortality in 2008. The present study visually determined the pathology scores of PCa specimens by taking into account five characteristics, including the hardness, color, plumpness, transparency and uniformity of specimens. The current study also aimed to identify the association between pathology scores and prostate specific antigen (PSA) levels, in order to reduce the complications caused by punctures and elevate the specimen positive rates. A total of 1,608 specimens from 268 patients were analyzed by one sonographer, one urologist and one pathologist. A standard pathological examination was performed on the PCa biopsy specimens and specimen scores were recorded under double-blinded conditions. A receiver operator characteristic curve identified a linear correlation between the visually determined score and PSA levels (r=0.255; P<0.001). Furthermore, logistic regression analysis indicated that the visually determined score and PSA were correlated with the diagnosis of PCa. Additionally, the authenticity of the visually determined score was higher than PSA in the diagnosis of PCa, with the best sensitivity and specificity of the visually determined scores used to predict PCa being 0.817 and 0.931, respectively.

Atorvastatin enhances radiosensitivity in hypoxia-induced prostate cancer cells related with HIF-1α inhibition.

Hypoxia could enhance radioresistance in prostate cancer cells through up-regulating HIF-1α, which could be inhibited by statins in several cancer cells. However, this effect of statins in prostate cancer remains unclear. In the present study, we aim to investigate the effect of atorvastatin on HIF-1α expression and radiosensitivity in prostate cancer cells. The hypoxia-induced human prostate cancer PC3 cells were generated by incubating with 5% O2 for 24 h. The cell viability and apoptosis were respectively analyzed by cell counting kit-8 (CCK-8) assay and flow cytometry. The HIF-1α protein expression was assessed by Western blotting. HIF-1α expression in PC3 cells was significantly increased after incubating with 5% O2 for 24 h. The viability of hypoxia-induced PC3 cells was inhibited by a higher dose of irradiation than control cells. The viability of hypoxia-induced PC3 cells were inhibited by astorvastatin with a higher concentration than control cells. Astorvastatin reduced the HIF-1α protein expression in hypoxia-induced PC3 cells, and induced apoptosis of both control and hypoxia-induced cells with and without irradiation. Atorvastatin could enhance radiosensitivity in hypoxia-induced prostate cancer cells, which may be related with inhibition of HIF-1α protein.

CIP2A mediates fibronectin-induced bladder cancer cell proliferation by stabilizing ß-catenin.

BACKGROUND: Fibronectin (FN) is associated with tumorigenesis and progression in bladder cancer, however, the underlying mechanisms causing this remain largely unknown. Furthermore, cancerous inhibitor of protein phosphatase 2A (CIP2A) has been shown to play important regulatory roles in cancer proliferation. Here, we investigated whether FN regulates CIP2A expression to promote bladder cancer cell proliferation. METHODS: The correlations of stromal FN with CIP2A and proliferating cell nuclear antigen (PCNA) expression were analyzed in a cohort bladder cancer patients. The roles of FN and CIP2A in regulating bladder cancer cell proliferation were evaluated in cell and animal models. Cycloheximide treatment was used to determine the effects of CIP2A on ß-catenin stabilization. The CIP2A-ß-catenin interaction was confirmed by immunofluorescence staining and co-immunoprcipitation. RESULTS: In this study, we found that stromal FN expression correlated positively with the levels of CIP2A and PCNA in bladder cancer tissues. Meanwhile, in human bladder cancer cell lines (T24 and J82), exogenous FN significantly promoted cell proliferation, however, CIP2A depletion inhibited this process. Furthermore, the interaction between CIP2A and ß-catenin enhanced the stabilization of ß-catenin, which was involved in FN-induced cell proliferation. In vivo, CIP2A depletion repressed FN-accelerated subcutaneous xenograft growth rates. CONCLUSIONS: These data reveal that CIP2A is a crucial mediator of FN-induced bladder cancer cell proliferation via enhancing the stabilization of ß-catenin. Promisingly, FN and CIP2A could serve as potential therapeutic targets for bladder cancer treatment.