Landscape of urine biomarkers for bladder cancer:molecular function,cell-of-origin,and bibliometric trend

Background:The effective management of bladder cancer(BCa)depends on the early diagnosis and surveillance.Previous studies have explored numerous urinary molecules as potential biomarkers of BCa.However,the molecular functions and cell-of-origin profiles of these biomarkers are yet to be elucidated.In this study,we aimed to provide a comprehensive overview of the landscape of urinary biomarker genes for BCa.Methods:We conducted an exhaustive literature search in PubMed,through which 555 biomarker genes were identified.We then analyzed the BCa single-cell atlas to infer the cellular origin of these BCa urine biomarker genes and performed functional enrichment analysis to gain insights into the functional molecular implications of these biomarkers.Results:These genes are involved in tumor proliferation,angiogenesis,cellmigration,and cell death and are predominantly expressed in epithelial and stromal cells.Interestingly,our analysis ofmultiomics tumor data revealed a discordance between tissue and urine in terms of differential methylation and RNA expression,suggesting that biomarker discovery for liquid biopsies should ideally begin with the analysis of bodily fluids rather than relying interest and that test strategies incorporating multiple molecular markers represent an ongoing trend.Conclusions:Collectively,our study has built a landscape of BCa urine biomarker genes,uncovered molecular insights into these biomarkers,and revealed the bibliometric trends in this field,which will contribute to the discovery of novel biomarkers in the future.

Biomarker and pathway analyses of urine metabolomics in dairy cows when corn stover replaces alfalfa hay

Background： Alfalfa hay and corn stover are different type of forages which can significantly impact a cow＇s lactation performance, but the underlying metabolic mechanism has been poorly studied. We used biomarker and pathway analyses to characterize related biomarkers and pathways based on urine metabolomics data from different forage treatments. Urine was col ected from 16 multiparous Holstein dairy cows fed alfalfa hay（AH, high-quality forage, n = 8） and corn stover（CS, low-quality forage, n = 8） respectively. Gas chromatography–time of flight/mass spectrometry（GC-TOF/MS） was performed to identify metabolites in urine and the metaboanalyst online platform was used to do biomarker and pathway analysis.Results： Hippuric acid（HUA） and N-methyl-glutamic（NML-Glu） indicated the most significant difference between the two diets, when statistical y validated by biomarker analysis. HUA was also validated by standard compound quantitative method and showed significant higher concentration in CS group than AH group（2.8282 vs. 0.0005 mg/mL; P 〈 0.01）.The significant negative correlation between milk yield and HUA（R^2= 0.459; P 〈 0.01） and significant positive correlation between milk yield and NML-Glu（R^2= 0.652; P 〈 0.01） were characterized. The pathway analysis revealed that these different metabolites were involved in 17 pathways including 7 influential pathways（pathway impact value 〉 0）： Tyr metabolism, starch and sucrose metabolism, amino sugar and nucleotide sugar metabolism, galactose metabolism,Phe, Tyr and Try biosynthesis, purine metabolism, and glycerolipid metabolism. Based on the metabolome view map,the Phe, Tyr and Try biosynthesis pathway exhibited the highest impact value（0.50）, and the Holm-Bonferroni multiple testing-based analysis revealed the most significant difference in the Tyr metabolism pathway（Holm P = 0.048）.Conclusions： The identified HUA and NML-Glu may serve as potential biomarkers for discriminating CS and AH diets and could be used as candidates for milk yield related mechanistic investigations. Integrated network pathways associated with related metabolites provide a helpful perspective for discovering the effectiveness of forage quality in lactation performance and provides novel insights into developing strategies for better utilization of CS and other low-quality forage in China.

Association of Increased Urine Brain Derived Neurotrophic Factor with Lower Urinary Tract Symptoms in Men with Benign Prostatic Hyperplasia

Urinary brain-derived neurotrophic factor（BDNF）, an ubiquitous neurotrophin, was found to rise in patients with benign prostatic hyperplasia（BPH）. We hypothesized that the urinary level of BDNF could be a potential biomarker for lower urinary tract symptoms（LUTS） in patients with BPH. Totally, 76 patients with BPH-caused LUTS and 32 male control subjects without BPH were enrolled. International Prostate Symptom Score（IPSS） was applied to assess the symptom severity of LUTS. Urodynamic tests were performed for the diagnosis of underlying detrusor overactivity（DO） in the patients with BPH. Urine samples were collected from all subjects. Urinary BDNF levels were measured using enzyme-linked immunosorbent assays and normalized by urinary creatinine（Cr） levels. Seventy-six BPH patients were divided into moderate LUTS group（n=51, 720） according to the IPSS. Of the 76 BPH patients, DO was present in 34（44.7%） according to the urodynamic test. The urinary BDNF/Cr levels were significantly higher in BPH patients with moderate LUTS（8.29±3.635, P〈0.0001） and severe LUTS（11.8±6.44, P〈0.0001） than normal controls（1.71±0.555）. Patients with severe LUTS tended to have higher urinary BDNF/Cr levels than patients with moderate LUTS（11.8±6.44 vs. 8.29±3.635, P=0.000）. The conditions of BPH with LUTS correlated with elevated urinary BDNF levels, and urinary BDNF levels were even higher in BPH-DO patients. The results of this study have provided evidence to suggest that urinary BDNF level test could evaluate the severity of LUTS in BPH patients, and BDNF level can be used as a biomarker