Prostate cancer (PC) is one of the most common male cancers worldwide. Until now, there is no consensus about using urinary metabolomic profiling as novel biomarkers to identify PC. In this study, urine samples from 50 PC patients and 50 non-cancerous individuals (control group) were collected. Based on ¹H nuclear magnetic resonance (¹H-NMR) analysis, 20 metabolites were identified. Subsequently, principal component analysis (PCA), partial least squares-differential analysis (PLS-DA) and ortho-PLS-DA (OPLS-DA) were applied to find metabolites to distinguish PC from the control group. Furthermore, Wilcoxon test was used to find significant differences between the two groups in metabolite urine levels. Guanidinoacetate, phenylacetylglycine, and glycine were significantly increased in PC, while L-lactate and L-alanine were significantly decreased. The receiver operating characteristics (ROC) analysis revealed that the combination of guanidinoacetate, phenylacetylglycine, and glycine was able to accurately differentiate 77% of the PC patients with sensitivity = 80% and a specificity = 64%. In addition, those three metabolites showed significant differences in patients stratified for Gleason score 6 and Gleason score ≥7, indicating potential use to detect significant prostate cancer. Pathway enrichment analysis using the KEGG (Kyoto Encyclopedia of Genes and Genomes) and the SMPDB (The Small Molecule Pathway Database) revealed potential involvement of KEGG “Glycine, Serine, and Threonine metabolism” in PC. The present study highlights that guanidinoacetate, phenylacetylglycine, and glycine are potential candidate biomarkers of PC. To the best knowledge of the authors, this is the first study identifying guanidinoacetate, and phenylacetylglycine as potential novel biomarkers in PC.

Background: A hallmark of Notch signaling is its variable role in tumor biology, ranging from tumor-suppressive to oncogenic effects. Until now, the mechanisms and functions of Notch pathways in bladder cancer (BCa) are still unclear. Methods: We used publicly available data from the GTEx and TCGA-BLCA databases to explore the role of the canonical Notch pathways in BCa on the basis of the RNA expression levels of Notch receptors, ligands, and downstream genes. For statistical analyses of cancer and non-cancerous samples, we used R software packages and public databases/webservers. Results: We found differential expression between control and BCa samples for all Notch receptors (NOTCH1, 2, 3, 4), the delta-like Notch ligands (DLL1, 3, 4), and the typical downstream gene hairy and enhancer of split 1 (HES1). NOTCH2/3 and DLL4 can significantly differentiate non-cancerous samples from cancers and were broadly altered in subgroups. High expression levels of NOTCH2/3 receptors correlated with worse overall survival (OS) and shorter disease-free survival (DFS). However, at long-term (>8 years) follow-up, NOTCH2 expression was associated with a better OS and DFS. Furthermore, the cases with the high levels of DLL4 were associated with worse OS but improved DFS. Pathway network analysis revealed that NOTCH2/3 in particular correlated with cell cycle, epithelial–mesenchymal transition (EMT), numbers of lymphocyte subtypes, and modulation of the immune system. Conclusions: NOTCH2/3 and DLL4 are potential drivers of Notch signaling in BCa, indicating that Notch and associated pathways play an essential role in the progression and prognosis of BCa through directly modulating immune cells or through interaction with cell cycle and EMT.

Bladder cancer (BCa) is one of the most common malignancies and has a relatively poor outcome worldwide. However, the molecular mechanisms and processes of BCa development and progression remain poorly understood. Therefore, the present study aimed to identify candidate genes in the carcinogenesis and progression of BCa. Five GEO datasets and TCGA-BLCA datasets were analyzed by statistical software R, FUNRICH, Cytoscape, and online instruments to identify differentially expressed genes (DEGs), to construct protein‒protein interaction networks (PPIs) and perform functional enrichment analysis and survival analyses. In total, we found 418 DEGs. We found 14 hub genes, and gene ontology (GO) analysis revealed DEG enrichment in networks and pathways related to cell cycle and proliferation, but also in cell movement, receptor signaling, and viral carcinogenesis. Compared with noncancerous tissues, TPM1, CRYAB, and CASQ2 were significantly downregulated in BCa, and the other hub genes were significant upregulated. Furthermore, MAD2L1 and CASQ2 potentially play a pivotal role in lymph nodal metastasis. CRYAB and CASQ2 were both significantly correlated with overall survival (OS) and disease-free survival (DFS). The present study highlights an up to now unrecognized possible role of CASQ2 in cancer (BCa). Furthermore, CRYAB has never been described in BCa, but our study suggests that it may also be a candidate biomarker in BCa.

Our goal was to find new diagnostic and prognostic biomarkers in bladder cancer (BCa), and to predict molecular mechanisms and processes involved in BCa development and progression. Notably, the data collection is an inevitable step and time-consuming work. Furthermore, identification of the complementary results and considerable literature retrieval were requested. Here, we provide detailed information of the used datasets, the study design, and on data mining. We analyzed differentially expressed genes (DEGs) in the different datasets and the most important hub genes were retrieved. We report on the meta-data information of the population, such as gender, race, tumor stage, and the expression levels of the hub genes. We include comprehensive information about the gene ontology (GO) enrichment analyses and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. We also retrieved information about the up- and down-regulation of genes. All in all, the presented datasets can be used to evaluate potential biomarkers and to predict the performance of different preclinical biomarkers in BCa.