Identification and Validation of Molecular Subtype and Prognostic Signature for Bladder Cancer Based on Neutrophil Extracellular Traps.

Neutrophil extracellular traps (NETs) could promote tumor growth and distant metastases. Molecular subtypes of bladder cancer were identified with consensus cluster analysis. A NETs-related prognostic signature was constructed with LASSO cox regression analysis. As a result, we identified three subtypes of bladder cancer, which had a distinct difference in prognosis, immune microenvironment, TIDE score, mRNAsi score and IC50 score. We also developed a prognostic signature based on 5 NETs-related genes, which had a good performance in clinical outcome prediction of bladder cancer. These results may provide more data about the vital role of NETs in bladder cancer.

Identification and verification of the pyroptosis-related prognostic signature and its associated regulatory axis in bladder cancer.

Background: Pyroptosis is an inflammatory form of cell death triggered by certain inflammasomes. Accumulating studies have shown the involvement of pyroptosis in the proliferation, invasion, and metastasis and prognosis of cancer. The prognostic value of pyroptosis-related genes (PRGs) and their association with immune infiltration in bladder cancer have not yet been elucidated. Methods: We performed a comprehensive analysis of the prognostic value and immune infiltrates of PRGs in bladder cancer using the TCGA dataset. qRT-PCR was also performed to verify our result. Results: Among 33 PRGs, 14 PRGs were upregulated or downregulated in bladder cancer tissue versus normal tissue. We also summarized copy number variations and somatic mutations of PRGs in bladder cancer. By using consensus clustering analysis of PRGs with prognostic significance, we divided the bladder cancer cohort into two subtypes significantly by different prognosis and immune infiltration. Using the LASSO Cox regression analysis, a prognostic signature including six PRGs was constructed for bladder cancer and the patients could be classified into a low- or high-risk group. Interestingly, this prognostic signature had a favorable performance for predicting the prognosis of bladder cancer patients. Moreover, further analysis demonstrated a significant difference in gender, tumor grade, clinical stage, TNM stage, immunoScore, and immune cell infiltration between the high- and low-risk groups in bladder cancer. We also identified an lncRNA SNHG14/miR-20a-5p/CASP8 regulatory axis in bladder cancer by constructing a ceRNA network. Conclusion: We identified a PRG-associated prognostic signature associated with the prognosis and immune infiltrates for bladder cancer and targeting pyroptosis may be an alternative approach for therapy. Further vivo and vitro experiments are necessary to verify these results.

The prognosis of different distant metastases pattern in malignant tumors of the adrenal glands: A population-based retrospective study.

INTRODUCTION: The present existing data on the association of metastatic sites and prognosis of patients with metastatic adrenal malignancy are limited. This study aims to investigate the impact of different distant metastases pattern on the survival of patients with adrenal malignancy. METHODS: A dataset from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) 18 Registries (2000-2017) was selected for a retrospective metastatic adrenal malignancy cohort study. There was information on distribution of metastatic lesions in bone, brain, liver, and lung in the SEER database. Kaplan-Meier analysis and nomogram analyses were applied to compare the survival distribution of cases. Univariate and multivariate cox regression models were used to analyze survival outcomes. RESULTS: From the SEER database, a total of 980 patients with primary metastatic adrenal malignancy from 2010 to 2017 were enrolled in this cohort study. Based on the initial metastatic sites, 42.3%, 38.4%, 30.5%, and 4.9% of patients were found bone, liver, lung, and brain metastasis, respectively. Patients who had a single site of distant metastases accounted for 52.6% (515/980) and had a better overall survival (OS) and cancer-specific survival (CSS) (both P < 0.001). In contrast with the tumor arising from the cortex, the tumor from the medulla showed better survival outcomes in both OS and CSS (P < 0.001). CONCLUSION: Different histological types possess various metastatic features and prognostic values. Understanding these differences may contribute to designing targeted pre-treatment assessment of primary metastatic adrenal malignancy and creating a personalized curative intervention.

The prognosis and clinicopathological features of different distant metastases patterns in renal cell carcinoma: analysis based on the SEER database.

Existing data on the prognosis and clinicopathological features of patients with metastatic renal cell carcinoma (mRCC) are limited. This study aims to investigate the prognostic value and clinicopathological features of different metastatic sites in patients with mRCC. A dataset from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database consisting of 18 registries (1973-2015) was selected for a retrospective mRCC cohort study. Information was included on the metastatic sites in lung, bone, liver, and brain. Kaplan-Meier analysis was applied to compare the survival distribution. Univariate and multivariate Cox regression models were used to analyze survival outcomes. From the SEER database, a total of 10,410 patients with primary mRCC from 2010 to 2015 were enrolled in this cohort study. Analysis indicated that 54.9%, 37.7%, 19.5%, and 10.4% of patients were found to have lung, bone, liver, and brain metastasis, respectively. There was a significantly higher risk for sarcomatoid RCC patients to develop liver metastasis as compared to patients with clear cell RCC. The median survival for patients with lung, bone, liver, or brain metastasis was 7 months, 7 months, 4 months, and 5 months, respectively. Various clinicopathological features and prognostic values are associated with different metastatic sites. Understanding these differences may enable targeted pre-treatment assessment of primary mRCC and personalized curative intervention for patients.

NF-κB inhibitor, BAY11-7082, suppresses M2 tumor-associated macrophage induced EMT potential via miR-30a/NF-κB/Snail signaling in bladder cancer cells.

BACKGROUND: Chronic inflammatory microenvironment has been shown to play a key role in initiating tumorigenesis and facilitating malignant progression. Primary tumors surrounded with and infiltrated by tumor-associated macrophages (TAMs) significantly promote the epithelial-to-mesenchymal transition (EMT) and distant metastasis in urothelial bladder cancer. METHODS: In this study, we aimed to explore the potential of targeting TAMs for the treatment of malignant bladder cancer. RESULTS: First, we found a higher number of TAMs, CD68 (pan-macrophage marker), and clever-1 (M2 macrophage marker) was associated with a higher pT category and grade in a cohort of 108 patients. In vitro assays showed that the co-culture of TAMs promoted the metastatic potential in HTB-1 and T24 by up-regulating EMT markers including Snail, VEGF and Vimentin, as well as oncogenic markers such as ß-catenin and NF-κB. More importantly, M2 co-cultured HTB-1 and T24 showed an increased level of metastatic microRNA, miR-30. Silencing of miR-30 resulted in the reduced metastatic potential, migration/invasion, in association with the decreased expression of Twist1 and Vimentin. The addition of BAY11-7082 into the TAM/cancer co-culture system significantly reduced the M2 phenotype and tumorigenic properties. Coincidentally, miR-30a level was significantly lowered in the presence of BAY11-7082. CONCLUSION: Our study demonstrated that AMs promoted metastatic potential of bladder cancer cells via promoting EMT through the increase of miR-30a. BAY11-7082 treatment suppressed both oncogenic and metastatic potential in bladder cancer cells while preventing the M2 polarization of TAMs.

Diagnostic performance of PCA3 and hK2 in combination with serum PSA for prostate cancer.

OBJECTIVES: The prostate cancer gene 3 (PCA3), human kallikrein 2, and miRNA-141 are promising prostate cancer (Pca) specific biomarkers. Our aim was to evaluate the detection of PCA3, human glandular kallikrein 2 (hk2), and miRNA-141 mRNA in peripheral blood of patients received prostate biopsy. What's more, we want to detect the value of combination of PSA (prostate specific antigen) in the early diagnosis of PCa. MATERIALS AND METHODS: Hundred patients were divided into 2 groups according to the results of pathologic diagnosis. Quantitative real-time PCR (qRT-PCR) was used to evaluate the mRNA of PCA3, hk2, and miRNA-141 in peripheral blood. At the same time, analyze those clinical outcomes used in the patients. We compared these different outcomes to evaluate the value of new molecular markers. RESULTS: The level of mRNA of PCA3, hK2, and miR-141 in Pca group were significantly higher than that in BPH. PSA had the highest sensitivity in predicting Pca diagnosis (76.7%); PCA3 had the highest specificity (82.5%). And the combination of PCA3, PSA, and hK2 improved area under the curve (AUC)-receiver operating characteristic (ROC) curve largely, especially those with PSA 4-10ng/mL. CONCLUSIONS: PCA3, hK2, and miRNA-141 were biomarkers of Pca with potential clinical application value, especially in patients with PSA gray area. Combining PCA3, PSA, and hK2 performed better than individual biomarkers alone in predicting Pca.

Effect of NQO1 C609T polymorphism on prostate cancer risk: a meta-analysis.

BACKGROUND: Some studies have found that the NAD(P)H: quinone oxidoreductase 1 (NQO1) SNP609 is associated with an increased risk for several malignancies. Numerous epidemiological studies have evaluated the association between the NQO1 C609T polymorphism and the risk of prostate cancer. However, the results of these studies have been conflicting. The aim of this study was to provide a more precise estimation of its relationship with prostate cancer using a meta-analysis. METHODS: Electronic searches of several databases were conducted for all publications on the association between the NQO1 C609T polymorphism and prostate cancer before May 2013. The odds ratio (OR) and its 95% confidence interval (CI) were used for statistical analysis. RESULTS: A total of six studies with 717 cases and 1,794 controls were included. No significant association was found between the NQO1 C609T polymorphism and prostate cancer risk in the total population analysis. In subgroup meta-analysis by ethnicity, a positive association was found in an Asian subgroup (T versus C, OR 1.337, 95% CI 1.014-1.763, P=0.040; TT + CT versus CC, OR 1.419, 95% CI 1.053-1.913, P=0.021). However, no significant association in any genetic models was observed in Caucasians. CONCLUSION: This meta-analysis showed that the NQO1 SNP609 T allele might be a risk factor for prostate cancer in Asians. However, this result should be verified by additional population-based studies with large sample sizes.

A meta-analysis of coffee intake and risk of urolithiasis.

OBJECTIVE: Epidemiologic studies have reported various results relating coffee to urolithiasis. A meta-analysis of cohort and case-control studies was conducted to pool the relative risk (RR) estimates of the association between coffee and urolithiasis. METHODS: Eligible studies were retrieved via both computer searches and review of references. We analyzed abstracted data with random effects models to obtain the summary RR estimates. A dose-response meta-analysis was performed for studies reporting categorical RR estimates for a series of exposure levels. RESULTS: A total of 6 studies (2 cohort and 4 case-control studies) on coffee intake were included in the meta-analysis. The pooled odds ratio (OR) showed a significant influence of the highest coffee consumption (OR = 0.70, 95% confidence interval 0.60-0.82) on the risk of urolithiasis. Coffee exhibited an inverse dose-response relationship with urolithiasis. In stratified analysis, a significant inverse association between coffee and urolithiasis was observed in study design, geographical region and gender subgroup. CONCLUSIONS: The overall current literature suggests that coffee intake is associated with a decreased risk of urolithiasis. Further efforts should be made to clarify the underlying biological mechanisms.