Efficiency of bladder-sparing strategies for bladder cancer: an umbrella review.

Bladder preservation (BP) has emerged as a clinical alternative to radical cystectomy (RC) for alleviating the substantial physical and psychological burden imposed on localized bladder cancer patients. Nevertheless, disparities persist in the comparative evaluations of BP and RC. We aimed to address the disparities between BP and RC. An umbrella review and meta-analysis were conducted to explore these disparities. We extracted data from meta-analyses and randomized controlled trials (RCTs) selected after searching PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews. Review Manager 5.4.0 and R x64 4.1.3 were used to evaluate the collected data. Our study included 11 meta-analyses and 3 RCTs. In terms of progression-free survival, all the meta-analyses reported that patients with localized bladder cancer who underwent BP exhibited outcomes comparable to those who underwent RC. Meta-analyses regarding the outcomes of cancer-specific survival (CSS) and overall survival (OS) are controversial. To solve these issues, we conducted a pooled analysis of CSS data, which supported the similarity of CSS between BP and RC with no significant heterogeneity [odds ratio (OR): 1.2; 95% confidence interval (CI): 0.71-2.02; I2 = 26%]. Similarly, the pooled OS results extracted from three RCTs indicated the comparability of OS between BP and RC with no significant heterogeneity (OR: 1.12; 95% CI: 0.41-3.07; I2 = 33%). A combination of umbrella review and meta-analysis results suggested that BP had survival rates comparable to those of RC. We suggest that BP may be a more eligible therapy than RC for patients with localized muscle-invasive bladder cancer. This conclusion warrants further validation through randomized controlled trials.

An endothelial-related prognostic index for bladder cancer patients.

BACKGROUND: Within the tumor microenvironment, endothelial cells hold substantial sway over bladder cancer (BC) prognosis. Herein, we aim to elucidate the impact of endothelial cells on BC patient outcomes by employing an integration of single-cell and bulk RNA sequencing data. METHODS: All data utilized in this study were procured from online databases. R version 3.6.3 and relevant packages were harnessed for the development and validation of an endothelial-associated prognostic index (EPI). RESULTS: EPI was formulated, incorporating six genes (CYTL1, FAM43A, GSN, HSPG2, RBP7, and SLC2A3). EPI demonstrated significant prognostic value in both The Cancer Genome Atlas (TCGA) and externally validated dataset. Functional results revealed a profound association between EPI and endothelial cell functionality, as well as immune-related processes. Our findings suggest that patients with low-risk EPI scores are more likely to respond positively to immunotherapy, as indicated by immune checkpoint activity, immune infiltration, tumor mutational burden, stemness index, TIDE, and IMvigor210 analyses. Conversely, individuals with high-risk EPI scores exhibited heightened sensitivity to cisplatin, docetaxel, and gemcitabine treatment regimens. CONCLUSION: We have effectively discerned pivotal genes from the endothelial cell perspective and constructed an EPI for BC patients, thereby offering promising prospects for precision medicine.

Identification of endothelial-related molecular subtypes for bladder cancer patients.

Background: Bladder cancer (BC) is a disease with significant heterogeneity and poor prognosis. The prognosis and therapeutic response of BC patients are significantly influenced by endothelial cells in the tumor microenvironment. In order to understand BC from the perspective of endothelial cells, we orchestrated molecular subtypes and identified key genes. Methods: Single-cell and bulk RNA sequencing data were extracted from online databases. R and its relative packages were used to analyze these data. Cluster analysis, prognostic value analysis, function analysis, immune checkpoints, tumor immune environment and immune prediction were conducted. Results: Five endothelial-related genes (CYTL1, FAM43A, HSPG2, RBP7, and TCF4) divided BC patients in the TCGA, GSE13507, and GSE32894 datasets into two clusters, respectively. In prognostic value analysis, patients in the cluster 2 were substantially associated with worse overall survival than those in the cluster 1 according to the results of TCGA, GSE13507 and GSE32894 datasets. In the results of functional analysis, the endothelial-related clusters was enriched in immune-related, endothelial-related and metabolism-related pathways. Samples in the cluster 1 had a statistically significant increase in CD4+ T cells and NK-cell infiltration. Cluster 1 was positively correlated with the cancer stem score and tumor mutational burden score. The results of immune prediction analysis indicated that 50.6% (119/235) of patients in the cluster 1 responded to immunotherapy, while the response rate in the cluster 2 decreased to 16.7% (26/155). Conclusion: In this study, we categorized and discovered distinctive prognosis-related molecular subtypes and key genes from the perspective of endothelial cells at the genetic level by integrating single-cell and bulk RNA sequencing data, primarily to provide a roadmap for precision medicine.

M7G-related molecular subtypes can predict the prognosis and correlate with immunotherapy and chemotherapy responses in bladder cancer patients.

BACKGROUND: N7-methylguanosine (m7G) is closely associated with tumor prognosis and immune response in many cancer types. The correlation between m7G and bladder cancer (BC) needs further study. We aimed to orchestrate molecular subtypes and identify key genes for BC from the perspective of m7G. METHODS: RNA-seq and clinical data of BC patients were extracted from TCGA and GSE13507 datasets. The patients were subtyped by "ConsensusClusterPlus" and "limma." The clusters were validated by the Kaplan‒Meier curves, univariable and multivariate Cox regression models, the concordance index, and calibration curves. The immunotherapy response was evaluated by immune checkpoints, immune infiltration, TIDE score, and IMvigor210 cohort. Genomics of Drug Sensitivity in Cancer was utilized to predict the chemotherapy response between the clusters. RESULTS: The m7G-related cluster was ultimately established by EIF4G1, NUDT11, NUDT10, and CCNB1. The independent prognostic value of the m7G-related cluster was validated by the TCGA and GSE13507 datasets. The cluster was involved in immune-associated pathways, such as neutrophil degranulation, antigen processing cross-presentation, and signaling by interleukins pathways. Meanwhile, cluster 2 was positively correlated with many immune checkpoints, such as CD274, CTLA4, HAVCR2, LAG3, PDCD1, and PDCD1LG2. The cluster 2 was significantly correlated with a higher TIDE score than the cluster 1. Furthermore, in the IMvigor210 cohort, patients in the cluster 1 had a higher response rate than those in the cluster 2. Patients in the cluster 2 were sensitive to many chemotherapies. CONCLUSIONS: We successfully determined molecular subtypes and identified key genes for BC from the perspective of m7G, thereby providing a roadmap for the evolution of immunotherapy and precision medicine.

Lymphocyte-to-Monocyte Ratio (LMR) During Induction Is a Better Predictor Than Preoperative LMR in Patients Receiving Intravesical Bacillus Calmette -Guerin for Non-Muscle-Invasive Bladder Cancer.

The prognostic value of the lymphocyte-to-monocyte ratio during induction (ILMR) remains unclear in non-muscle-invasive bladder cancer (NMIBC) patients receiving Bacillus Calmette-Guérin (BCG). We aimed to determine and compare the prognostic value of the ILMR, preoperative lymphocyte-to-monocyte ratio (PLMR) and their dynamic changes (PILMR). This study collected the data from NMIBC patients receiving BCG treatment in our institution. The prognostic value of the PLMR, ILMR and PILMR was analyzed by the Kaplan-Meier method and Cox proportional hazard regression models. The concordance index and receiver operating characteristic curve analysis were employed to compare the prognostic value of these three factors. Our study enrolled 197 patients. These patients included 170 male patients, and the mean age was 64.17 years. During the follow-up time, 85 patients experienced recurrence, and 55 patients experienced progression. According to the results of COX multivariable analysis, PLMR (P=0.011) and ILMR (P<0.001) could independently predict the recurrence of NMIBC patients receiving BCG. Meanwhile, ILMR (P=0.001) and PILMR (P=0.036) were also the independent prognostic factors of progression. Compared with PLMR and PILMR, ILMR was associated with better accuracy for NMIBC patients receiving BCG. This study first found that the ILMR could independently predict the prognosis of NMIBC patients receiving BCG. Furthermore, we also identified that ILMR was associated with higher prognostic value than PLMR and PILMR, which might help to select an optimal treatment schedule for patients with NMIBC.

A novel prosodic-information synthesizer based on recurrent fuzzy neural network for the Chinese TTS system.

In this paper, a new technique for the Chinese text-to-speech (TTS) system is proposed. Our major effort focuses on the prosodic information generation. New methodologies for constructing fuzzy rules in a prosodic model simulating human's pronouncing rules are developed. The proposed Recurrent Fuzzy Neural Network (RFNN) is a multilayer recurrent neural network (RNN) which integrates a Self-cOnstructing Neural Fuzzy Inference Network (SONFIN) into a recurrent connectionist structure. The RFNN can be functionally divided into two parts. The first part adopts the SONFIN as a prosodic model to explore the relationship between high-level linguistic features and prosodic information based on fuzzy inference rules. As compared to conventional neural networks, the SONFIN can always construct itself with an economic network size in high learning speed. The second part employs a five-layer network to generate all prosodic parameters by directly using the prosodic fuzzy rules inferred from the first part as well as other important features of syllables. The TTS system combined with the proposed method can behave not only sandhi rules but also the other prosodic phenomena existing in the traditional TTS systems. Moreover, the proposed scheme can even find out some new rules about prosodic phrase structure. The performance of the proposed RFNN-based prosodic model is verified by imbedding it into a Chinese TTS system with a Chinese monosyllable database based on the time-domain pitch synchronous overlap add (TD-PSOLA) method. Our experimental results show that the proposed RFNN can generate proper prosodic parameters including pitch means, pitch shapes, maximum energy levels, syllable duration, and pause duration. Some synthetic sounds are online available for demonstration.