Biomarkers For Diagnosis Of Bladder Cancer Research Articles

Comprehensive proteomics and platform validation of urinary biomarkers for bladder cancer diagnosis and staging

BackgroundBladder cancer (BC) is among the most common cancers diagnosed in men in the USA. The current gold standards for the diagnosis of BC are invasive or lack the sensitivity to correctly identify the disease.MethodsAn aptamer-based screen analyzed the expression of 1317 proteins in BC compared to urology clinic controls. The top hits were subjected to systems biology analyses. Next, 30 urine proteins were ELISA-validated in an independent cohort of 68 subjects. Three of these proteins were next validated in an independent BC cohort of differing ethnicity.ResultsSystems biology analysis implicated molecular functions related to the extracellular matrix, collagen, integrin, heparin, and transmembrane tyrosine kinase signaling in BC susceptibility, with HNF4A and NFKB1 emerging as key molecular regulators. STEM analysis of the dysregulated pathways implicated a functional role for the immune system, complement, and interleukins in BC disease progression. Of 21 urine proteins that discriminated BC from urology clinic controls (UC), urine d-dimer displayed the highest accuracy (0.96) and sensitivity of 97%. Furthermore, 8 urine proteins significantly discriminated MIBC from NMIBC (AUC = 0.75–0.99), with IL-8 and IgA being the best performers. Urine IgA and fibronectin exhibited the highest specificity of 80% at fixed sensitivity for identifying advanced BC.ConclusionsGiven the high sensitivity (97%) of urine d-dimer for BC, it may have a role in the initial diagnosis or detection of cancer recurrence. On the other hand, urine IL-8 and IgA may have the potential in identifying disease progression during patient follow-up. The use of these biomarkers for initial triage could have a significant impact as the current cystoscopy-based diagnostic and surveillance approach is costly and invasive when compared to a simple urine test.

Recent development of urinary biomarkers for bladder cancer diagnosis and monitoring

AbstractUrine‐based liquid biopsy has emerged as a non‐invasive and effective tool for early screening and diagnosis of bladder cancer. This review provides a comprehensive overview of the current urine‐based biomarkers and methods for the detection and monitoring of bladder cancer. We focus on biomarkers including tumour DNAs, proteins, microbiome, tumour RNAs, long non‐coding RNAs, transfer RNA‐derived fragments, messenger RNAs, microRNAs, circular RNAs, exosomes and extrachromosomal circular DNA.

Urine exosomes as biomarkers in bladder cancer diagnosis and prognosis: From functional roles to clinical significance.

Bladder cancer is one of the top ten most common cancers and top ten causes of cancer death globally. 5-year survival rates have decreased in Australia from 66% to 55% in the past three decades. The current gold standard for diagnosis is cystoscopy. However, cystoscopies are an invasive and health-resource intensive procedure which has sub-optimal sensitivity for flat lesions such as CIS (carcinoma in situ) and low specificity for differentiating inflammation from cancer - hence requiring biopsies under anesthesia. Frequent and life-long surveillance cystoscopy is required for most patients since there are high rates of progression and local recurrence in high-risk non-muscle invasive cancer (NMIBC) as well as poor outcomes associated with delayed detection of muscle-invasive bladder cancer (MIBC). There is an unmet need for a non-invasive test to provide better discrimination and risk-stratification of bladder cancer which could aid clinicians by improving patient selection for cystoscopy; enhanced risk stratification methods may guide the frequency of surveillance cystoscopies and inform treatment choices. Exosomes, which are nano-sized extracellular vesicles containing genetic material and proteins, have been shown to have functional roles in the development and progression of bladder cancer. Exosomes have also been demonstrated to be a robust source of potential biomarkers for bladder cancer diagnosis and prognosis and may also have roles as therapeutic agents. In this review, we summarize the latest evidence of biological roles of exosomes in bladder cancer and highlight their clinical significance in bladder cancer diagnosis, surveillance and treatment.

Biomarkers for bladder cancer diagnosis, prognosis, monitoring and treatment.

Biomarkers for bladder cancer diagnosis, prognosis, monitoring and treatment.

Evaluation of Serum miR-17-92 Cluster as Noninvasive Biomarkers for Bladder Cancer Diagnosis.

Previous studies have shown that the miR-17-92 cluster is involved in the occurrence and development of bladder cancer. However, the role of serum miR-17-92 cluster in the diagnosis of bladder cancer has not been studied. In the present study, we evaluated the expression of miR-17-92 cluster members in bladder cancer tissues by analyzing 428 cases from TCGA database. Next, we collected the sera of 74 bladder cancer patients and 90 controls, and used qRT-PCR to detect the relative expression of the cluster. The results showed that the expression of the cluster members in the sera of patients were significantly higher than that of the controls, and they were positively correlated with the clinical stage and pathological grade of the patients. We evaluated their ability to diagnose bladder cancer using ROC, of which miR-92a-3p (AUC = 0.902), miR-17-5p (AUC = 0.845) and miR-20a-5p (AUC = 0.806) were the most prominent. Finally, we established a diagnostic model by logistic regression (AUC = 0.969). We further validated the results of the study using another dataset from the GEO database. Moreover, we evaluated the prognostic value of the cluster. The results revealed that miR-20a-5p was correlated with recurrence of bladder cancer. In summary, the present study validated the overexpression of serum miR-17-92 cluster in bladder cancer. The model composed of the three cluster members were confirmed to be a promising noninvasive biomarker for bladder cancer diagnosis.

Next-generation Proteomics-Based Discovery, Verification, and Validation of Urine Biomarkers for Bladder Cancer Diagnosis.

PurposeWe aimed to identify, verify, and validate a multiplex urinary biomarker-based prediction model for diagnosis and surveillance of urothelial carcinoma of bladder, using high-throughput proteomics methods.Materials and MethodsLabel-free quantification of data-dependent and data-independent acquisition of 12 and 24 individuals was performed in each of the discovery and verification phases using mass spectrometry, simultaneously using urinary exosome and proteins. Based on five scoring system based on proteomics data and statistical methods, we selected eight proteins. Enzyme-linked immunosorbent assay on urine from 120 patients with bladder mass lesions used for validation. Using multivariable logistic regression, we selected final candidate models for predicting bladder cancer.ResultsComparing the discovery and verification cohorts, 38% (50/132 exosomal differentially expressed proteins [DEPs]) and 44% (109/248 urinary DEPs) are consistent at statistically significance, respectively. The 20 out of 50 exosome proteins and 27 out of 109 urinary proteins were upregulated in cancer patients. From eight selected proteins, we developed two diagnostic models for bladder cancer. The area under the receiver operating characteristic curve (AUROC) of two models were 0.845 and 0.842, which outperformed AUROC of urine cytology.ConclusionThe results showed that the two diagnostic models developed here were more accurate than urine cytology. We successfully developed and validated a multiplex urinary protein-based prediction, which will have wide applications for the rapid diagnosis of urothelial carcinoma of the bladder. External validation for this biomarker panel in large population is required.

Combination of urinary fibrinogen β-chain and tyrosine-phosphorylated proteins for the detection of bladder cancer.

Aim:To evaluate the performance of urinary fibrinogen β-chain (FBC) – either alone or associated with urinary tyrosine-phosphorylated proteins (UPY) – as bladder cancer (BCa) diagnostic biomarker.Materials & methods:164 subjects were tested.Results:Significantly different FBC and UPY levels were found between BCa patients and controls, as well as between low-grade and high-grade cancers. The diagnostic accuracy was 0.84 for FBC and 0.87 for UPY. The combination of FBC and UPY improved the accuracy to 0.91. The addition of clinical variables (age, gender, and smoking habit) to FBC and UPY into a model for BCa prediction significantly improved the accuracy to 0.99. The combination of FBC and UPY adjusted for clinical variables associates with the highest sensitivity and good specificity.Conclusion:Urinary FBC and UPY could be used as biomarkers for BCa diagnosis.

Urine Biomarkers for the Diagnosis of Bladder Cancer: a Network Meta-Analysis.

To identify effective urine biomarkers for bladder cancer diagnosis. This meta-analysis was conducted following the guidelines of the Meta-Analyses (PRISMA) statement. Relevant studies were searched from the PubMed, Embase, and Cochrane Library databases. Heterogeneity tests were performed using Q statistics and I2 tests to determine the use of the random or fixed effects model. A direct comparison meta-analysis and network meta-analysis were conducted. The effect values are presented as odds ratios and 95% confidence intervals. Sensitivity analysis and consistency tests were performed. Fifty-eight studies with 12,038 participants were included. Direct comparison meta-analysis showed statistically significant differences in bladder cancer antigen (BTA) trak vs. nuclear matrix protein 22 (NMP22), BTA stat vs. urine cytology (UC), and fluorescence in situ hybridization (FISH) vs. UC, among the sensitivity indicators. Among the specificity indicators, there were statistically significant differences in BTA trak vs. UC, ImmunoCyt (immunocyte) vs. NMP22, and BTA stat vs. FISH. Among the positive predictive indicators, NMP22 vs. UC, BTA stat vs. UC, and FISH vs. NMP22 showed statistically significant differences. Among the negative predictive indicators, the differences in FISH vs. UC, FISH vs. NMP22, and hyaluronidase 1 (HYAL-1) vs. UC were statistically significant. Among the accuracy indicators, FISH vs. NMP22, FISH vs. UC, and HYAL-1 vs. UC showed statistically significant differences. Network meta-analysis showed that HYAL-1, urothelial carcinoma associated 1 (UCA1) and survivin had the highest sensitivity, while UC had the lowest sensitivity. The specificity of UC, FISH, and HYAL-1 was the highest, while that of UCA1 was the lowest. In terms of positive predictive indicators, UC, FISH, and HYAL-1 had the highest positive predictive value, while the BTA group had the lowest positive predictive value. In terms of negative predictive indicators, HYAL-1, UCA1, and survivin had the highest negative predictive value, while UC had the lowest negative predictive value. In terms of accuracy indicators, HYAL-1, UCA1, and survivin had the highest accuracy, while UC had the lowest accuracy. HYAL-1 and survivin are suitable urine biomarkers for bladder cancer diagnosis.

The Roles of CircRNAs in Bladder Cancer: Biomarkers, Tumorigenesis Drivers, and Therapeutic Targets.

Bladder cancer (BCa) is the most prevalent malignancy of the urinary system. Circular RNAs (circRNAs), a novel subtype of non-coding RNAs, play a crucial role in physiological and developmental processes. CircRNAs mainly function as regulators of splicing process and transcription, microRNA sponges, and protein brackets. Recent advances in understanding the pathogenesis of BCa have led to the identification of an abundance of dysregulated circRNAs associated with BCa. These aberrantly expressed circRNAs eventually lead to abnormalities in biological, genetic, and epigenetic information. In this review, we introduce the potential of circRNAs as biomarkers for BCa diagnosis and prognosis. Notably, diverse mechanisms have been proposed for circRNAs driving carcinogenesis, including increasing cell proliferation, promoting invasive and migratory capacity, enhancing endothelial–mesenchymal transition, sustaining stemness, and enabling resistance to chemotherapy. Importantly, a full understanding of circRNA mechanisms is needed to mine promising therapeutic approaches for targeting BCa. In this paper, we present the latest advances in circRNAs and systemically summarize the characteristics and mechanisms of circRNAs in BCa, providing potential perspectives for BCa treatment.

Combination of Urine Exosomal mRNAs and lncRNAs as Novel Diagnostic Biomarkers for Bladder Cancer.

BackgroundThe recent discovery of miRNAs and lncRNAs in urine exosomes has emerged as promising diagnostic biomarkers for bladder cancer (BCa). However, mRNAs as the direct products of transcription has not been well evaluated in exosomes as biomarkers for BCa diagnosis. The purpose of this study was to identify tumor progression-related mRNAs and lncRNAs in urine exosomes that could be used for detection of BCa.MethodsRNA-sequencing was performed to identify tumor progression-related biomarkers in three matched superficial tumor and deep infiltrating tumor regions of muscle-invasive bladder cancer (MIBC) specimens, differently expressed mRNAs and lncRNAs were validated in TCGA dataset (n = 391) in the discovery stage. Then candidate RNAs were chosen for evaluation in urine exosomes of a training cohort (10 BCa and 10 healthy controls) and a validation cohort (80 BCa and 80 healthy controls) using RT-qPCR. The diagnostic potential of the candidates were evaluated by receiver operating characteristic (ROC) curves.ResultsRNA sequencing revealed 8 mRNAs and 32 lncRNAs that were significantly upregulated in deep infiltrating tumor region. After validation in TCGA database, 10 markedly dysregulated RNAs were selected for further investigation in urine exosomes, of which five (mRNAs: KLHDC7B, CASP14, and PRSS1; lncRNAs: MIR205HG and GAS5) were verified to be significantly dysregulated. The combination of the five RNAs had the highest AUC to disguising the BCa (0.924, 95% CI, 0.875–0.974) or early stage BCa patients (0.910, 95% CI, 0.850 to 0.971) from HCs. The expression levels of these five RNAs were correlated with tumor stage, grade, and hematuria degrees.ConclusionsThese findings highlight the potential of urine exosomal mRNAs and lncRNAs profiling in the early diagnosis and provide new insights into the molecular mechanisms involved in BCa.

Apolipoprotein A1 as a novel urinary biomarker for diagnosis of bladder cancer: A systematic review and meta-analysis.

Introduction:The emergence of urinary biomarkers for bladder cancer diagnosis could provide a reliable and less invasive diagnostic method. It could be also used as an adjuvant to the current gold standards of cytology and cystoscopy to improve diagnostic accuracy and decrease the percentage of false positives.Methods:We searched PubMed, SCOPUS, and Web of Science up to March 18, 2020. We selected four studies that assessed the diagnostic accuracy of urinary apolipoprotein A1 (ApoA-1) in detecting bladder cancer and met the inclusion and exclusion criteria. Two authors independently extracted the data and performed quality assessment of the studies.Results:Four studies with 771 participants were selected; 417 were bladder cancer patients and 354 were controls. Bladder cancer was either transitional cell carcinoma or squamous cell carcinoma, the stages varied between Ta to T3, and the grades varied between G1 and G3. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 90.7%, 90%, 9.478, 0.1, and 99.424, respectively. Summary receiver operating characteristic curve showed an area under the curve of 0.9544 and Q* index of 0.8965.Conclusions:ApoA-1 showed high sensitivity and specificity, so it could be a useful biomarker in diagnosis of bladder cancer.

Research Progress of Urine Biomarkers in the Diagnosis, Treatment, and Prognosis of Bladder Cancer.

Bladder cancer (BC) is one of the most common tumor with high incidence. Relative to other cancers, BC has a high rate of recurrence, which results in increased mortality. As a result, early diagnosis and life-long monitoring are clinically significant for improving the long-term survival rate of BC patients. At present, the main methods of BC detection are cystoscopy and biopsy; however, these procedures can be invasive and expensive. This can lead to patient refusal and reluctance for monitoring. There are several BC biomarkers that have been approved by the FDA, but their sensitivity, specificity, and diagnostic accuracy are not ideal. More research is needed to identify suitable biomarkers that can be used for early detection, evaluation, and observation. There has been heavy research in the proteomics and genomics of BC and many potential biomarkers have been found. Although the advent of metabonomics came late, with the recent development of advanced analytical technology and bioinformatics, metabonomics has become a widely used diagnostic tool in clinical and biomedical research. It should be emphasized that despite progress in new biomarkers for BC diagnosis, there remains challenges and limitations in metabonomics research that affects its translation into clinical practice. In this chapter, the latest literature on BC biomarkers was reviewed.

Matrix Metalloproteinase 11 is a Potential Biomarker in Bladder Cancer Diagnosis and Prognosis.

PurposeBladder cancer is one of the leading causes of cancer death all over the world, and half of patients are diagnosed at advanced stages with poor therapeutic response. Thus, developing new biomarkers for bladder cancer diagnosis and prognosis is urgently needed.Materials and MethodsBioinformatic and gene ontology (GO) analysis were employed to screen highly upregulated and secretory tumor markers in the TCGA BLCA cohort. IHC in tissue microarray and ELISA in cancer cell culture medium were used to validate the expression of putative biomarkers in bladder cancer. Bisulfite sequencing was used to detect DNA methylation status in the promoter of putative genes.ResultsIn this study, MMP11 is first identified as one of the most differentially expressed genes (DEGs) in bladder cancer by meta-analysis in a TCGA bladder cancer cohort. The strong upregulation of MMP11 is confirmed at protein levels in both bladder cancer patients and cell lines. Mechanistic studies reveal that MMP11 promoter hypomethylation, but not genomic amplification or mutation, accounts for its enhanced expression in bladder cancer both in vitro and in vivo. Moreover, clinicopathological analysis indicates that MMP11 upregulation is associated with the tumor progression and poor survival in bladder cancer patients.DiscussionThese findings suggest that MMP11, as a secretory protein, is a promising biomarker for diagnosis and prognosis in bladder cancer.

Biomarkers for Bladder Cancer Diagnosis and Surveillance: A Comprehensive Review.

Bladder cancer (BC) ranks as the sixth most prevalent cancer in the world, with a steady rise in its incidence and prevalence, and is accompanied by a high morbidity and mortality. BC is a complex disease with several molecular and pathological pathways, thus reflecting different behaviors depending on the clinical staging of the tumor and molecular type. Diagnosis and monitoring of BC is mainly performed by invasive tests, namely periodic cystoscopies; this procedure, although a reliable method, is highly uncomfortable for the patient and it is not exempt of comorbidities. Currently, there is no formal indication for the use of molecular biomarkers in clinical practice, even though there are several tests available. There is an imperative need for a clinical non-invasive testing for early detection, disease monitoring, and treatment response in BC. In this review, we aim to assess and compare different tests based on molecular biomarkers and evaluate their potential role as new molecules for bladder cancer diagnosis, follow-up, and treatment response monitoring.

Analysis of ceRNA network identifies prognostic circRNA biomarkers in bladder cancer.

Bladder cancer remains a very challenging disease to treat with the high rates of recurrence and progression associated with current therapies. Although the association between bladder cancer pathology and circRNAs remains undetermined, circRNAs signatures may be useful as prognostic and predictive factors and clinical tools for assessing disease state and outcome. This study investigates if these circRNAs can be used as biomarkers for bladder cancer diagnosis. Using bioinformatics method to analysis GEO databases (GSE37815, GSE39093, GSE97239, and GSE92675) for differentially expressed RNAs in bladder cancer and normal bladder tissues were screened from. The related volcanic maps and the interaction network maps of differentially expressed RNAs were drawn, and the mRNA-miRNA and miRNA-circRNA interaction were predicted to establish mRNA-miRNA-circRNA competitive endogenous RNA (ceRNA) network. The differential circRNAs related to prognosis of bladder cancer patients were screened based on the influence of miRNA interacting with the circRNA above on survival rate. The expression of miRNA (hsa-mir-214), circRNA (hsa_circ_0076704, hsa_circ_0081963, hsa_circ_0001361) in bladder cancer tissues, adjacent tissues, bladder cancer cells and normal bladder epithelial cells were validated by qRT-PCR. Kaplan Meier curve analysis confirmed the relationship between circRNA (hsa_circ_0076704) and overall survival and prognosis of bladder cancer patients. Through database screening and analysis, we found 19231 differentially expressed genes, 847 differentially expressed miRNAs, 7282 differentially expressed circRNAs. The establishment of ceRNA network consisted of 28 DERNAs (differentially- expressed RNAs), 12 Demi-RNAs and 12 DEcircRNAs. Further prognostic analysis showed that circRNA interacted miRNA hsa-miR-106b, hsa-miR-145 and hsa-miR-214 were associated with overall survival in patients with bladder cancer (P < 0.05). Among them, hsa_circ_0076704, hsa_circ_0081963 and hsa_circ_0001361 are potential circRNA related to OS in bladder cancer and expressed in bladder cancer. The expression of hsa-mir-214 was contrary. Further Kaplan Meier survival analysis showed that hsa_circ_0076704 had significant prognostic value (P < 0.05). In conclusion, hsa_circ_0076704 is independent prognostic factor for bladder cancer.

New Insights in Bladder Cancer Diagnosis: Urinary miRNAs and Proteins.

Bladder cancer is the 10th-most common cancer worldwide. The diagnosis and follow-up of patients require costly invasive methods and due to these expenses, bladder cancer continues to be one of the expensive malignancies. Early diagnosis is crucial in bladder cancer as it is in other cancers; therefore, non-invasive biomarkers for early diagnosis are very important. In this review, we aimed to focus on the most recent investigations on potential urinary micro RNA (miRNA) and protein biomarkers for bladder cancer diagnosis and their associated pathways. Studies performed by different groups were compiled and the biomarker properties of various proteins and miRNAs in the urine of bladder cancer patients were evaluated. Key studies were obtained by searching keywords “bladder cancer, urinary miRNA, urinary protein, urinary biomarker”. Targets and the pathways of the miRNAs and proteins were analyzed according to mirBase Catalogue and Panther Database. The major pathways that are targeted by aberrantly expressed miRNAs are Cholecystokinin receptor (CCKR), p53, Wnt signaling pathway, and feedback loops. We hereby conclude that urinary micro RNAs and proteins are promising candidates for bladder cancer diagnosis. It should be noted that urine collection, storage conditions, choice of fraction, and normalization strategies should be standardized.

Downregulation of hsa_circ_0000285 serves as a prognostic biomarker for bladder cancer and is involved in cisplatin resistance.

Bladder cancer remains a very challenging disease to treat with the high rates of recurrence and progression associated with current therapies. Although the association between bladder cancer pathology and circRNAs remains undetermined, circRNAs signatures may be useful as prognostic and predictive factors and clinical tools for assessing disease state, treatment response and outcome. This study investigates if these circRNAs can be used as biomarkers for bladder cancer diagnosis and predicting treatment response. Herein, qPCR measured the expression of hsa_circRNA_100783, hsa_circ_0000285 and hsa_circRNA_100782 in bladder cancer tissues. It was established that sa_circ_0000285, but not hsa_circRNA_100782 and hsa_circRNA_10078, are significantly reduced in bladder cancer tissues and serum compared to adjacent tissues and healthy controls. Moreover, hsa_circ_0000285 expression was lower in cisplatin-resistant bladder cancer patients than in those who were cisplatin-sensitive. Here, hsa_circ_0000285 was associated with tumor size (p<0.001), differentiation (p<0.001), lymph node metastasis (p=0.038), distant metastasis (p=0.004) and TNM stage (p=0.013). Further analysis showed that hsa_circ_0000285 would be an independent prognostic factor for bladder cancer patient outcome. In conclusion, our study indicates hsa_circ_0000285 may be a novel biomarker for bladder cancer because of its involvement in bladder cancer chemo-sensitivity.

Systematic verification of bladder cancer-associated tissue protein biomarker candidates in clinical urine specimens.

Bladder cancer biomarkers currently approved by the Food and Drug Administration are insufficiently reliable for use in non-invasive clinical diagnosis. Verification/validation of numerous biomarker candidates for BC detection is a crucial bottleneck for novel biomarker development. A multiplexed liquid chromatography multiple-reaction-monitoring mass spectrometry assay of 122 proteins, including 118 up-regulated tissue proteins, two known bladder cancer biomarkers and two housekeeping gene products, was successfully established for protein quantification in clinical urine specimens. Quantification of 122 proteins was performed on a large cohort of urine specimens representing a variety of conditions, including 142 hernia, 126 bladder cancer, 67 hematuria, and 59 urinary tract infection samples. ANXA3 (annexin A3) and HSPE1 (heat shock protein family E member 1), which showed the highest detection frequency in bladder cancer samples, were selected for further validation. Western blotting showed that urinary ANXA3 and HSPE1 protein levels were higher in bladder cancer samples than in hernia samples, and enzyme-linked immunosorbent assays confirmed a higher urinary concentration of HSPE1 in bladder cancer than in hernia, hematuria and urinary tract infection. Immunohistochemical analyses showed significantly elevated levels of HSPE1 in tumor cells compared with non-cancerous bladder epithelial cells, suggesting that HSPE1 could be a useful tumor tissue marker for the specific detection of bladder cancer. Collectively, our findings provide valuable information for future validation of potential biomarkers for bladder cancer diagnosis.

Discovery and validation of potential urinary biomarkers for bladder cancer diagnosis using a pseudotargeted GC-MS metabolomics method.

Bladder cancer (BC) is the second most prevalent malignancy in the urinary system and is associated with significant mortality; thus, there is an urgent need for novel noninvasive diagnostic biomarkers. A urinary pseudotargeted method based on gas chromatography–mass spectrometry was developed and validated for a BC metabolomics study. The method exhibited good repeatability, intraday and interday precision, linearity and metabolome coverage. A total of 76 differential metabolites were defined in the discovery sample set, 58 of which were verified using an independent validation urine set. The verified differential metabolites revealed that energy metabolism, anabolic metabolism and cell redox states were disordered in BC. Based on a binary logistic regression analysis, a four-biomarker panel was defined for the diagnosis of BC. The area under the receiving operator characteristic curve was 0.885 with 88.0% sensitivity and 85.7% specificity in the discovery set and 0.804 with 78.0% sensitivity and 70.3% specificity in the validation set. The combinatorial biomarker panel was also useful for the early diagnosis of BC. This approach can be used to discriminate non-muscle invasive and low-grade BCs from healthy controls with satisfactory sensitivity and specificity. The results show that the developed urinary metabolomics method can be employed to effectively screen noninvasive biomarkers.

The Use of Biomarkers for Bladder Cancer Diagnosis and Surveillance

Bladder cancer - a propensity that is associated with high recurrence and mortality rates. Various molecular alterations are reflected by diverse cellular morphological manifestations and vast tumor heterogeneity. Many biomarkers have been described that have undergone clinical trials and are approved for clinical use, but most still remain investigational. The question how molecular markers can support surveillance of different patient groups is still a matter of controversy. However, it can be expected that major advancement in the understanding of molecular pathways involved in urothelial carcinogenesis will enable improved patient management. The scope of this review is to discuss the established diagnostic tests and urinary biomarkers and their application for screening and surveillance of bladder cancer.