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


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          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.


          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.


          Urinary FBC and UPY could be used as biomarkers for BCa diagnosis.

          Lay abstract

          This research has developed and validated a highly accurate predictive model for BCa diagnosis based on the combination of two urinary biomarkers, fibrinogen β-chain (FBC), and urinary tyrosine-phosphorylated proteins (UPY), and some clinical variables (age, gender and smoking habit). If the preliminary promising results will be confirmed by external validations and prospective trials in selected clinical scenarios, our model could be transferred to clinical practice for screening of high-risk population.

          Graphical abstract

          Most cited references29

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          European Association of Urology Guidelines on Non-muscle-invasive Bladder Cancer (TaT1 and Carcinoma In Situ) - 2019 Update

          This overview presents the updated European Association of Urology (EAU) guidelines for non-muscle-invasive bladder cancer (NMIBC), TaT1, and carcinoma in situ (CIS).
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            Fibrinogen synthesized by cancer cells augments the proliferative effect of fibroblast growth factor-2 (FGF-2).

            Fibroblast growth factor (FGF)-2 is a critical growth factor in normal and malignant cell proliferation and tumor-associated angiogenesis. Fibrinogen and fibrin bind to FGF-2 and modulate FGF-2 functions. Furthermore, we have shown that extrahepatic epithelial cells are capable of endogenous production of fibrinogen. Herein we examined the role of fibrinogen and FGF-2 interactions on prostate and lung adenocarcinoma cell growth in vitro. Cell proliferation was measured by (3)H-thymidine uptake and the specificity of FGF-2-fibrinogen interactions was measured using wild-type and mutant FGF-2s, fibrinogen gamma-chain (FGG) RNAi and co-immunoprecipitation. Metabolic labeling, immunopurification and fluorography demonstrated de novo fibrinogen production. FGF-2 stimulated DU-145 cell proliferation, whereas neither FGF-2 nor fibrinogen affected the growth of PC-3 or A549 cells. Fibrinogen augmented the proliferative effect of FGF-2 on DU-145 cells. The role of fibrinogen in FGF-2-enhanced DNA synthesis was confirmed using an FGF-2 mutant that exhibits no binding affinity for fibrinogen. FGG transcripts were present in PC-3, A549 and DU-145 cells, but only PC-3 and A549 cells produced detectable levels of intact protein. RNAi-mediated knockdown of FGG expression resulted in decreased production of fibrinogen protein and inhibited (3)H-thymidine uptake in A549 and PC-3 cells by 60%, which was restored by exogenously added fibrinogen. FGF-2 and fibrinogen secreted by the cells were present in the medium as a soluble complex, as determined by coimmunoprecipitation studies. These data indicate that endogenously synthesized fibrinogen promotes the growth of lung and prostate cancer cells through interaction with FGF-2.
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              An up-to-date catalog of available urinary biomarkers for the surveillance of non-muscle invasive bladder cancer

              Objectives With the advent of novel genomic and transcriptomic technologies, new urinary biomarkers have been identified and tested for bladder cancer (BCa) surveillance. To summarize the current status of urinary biomarkers for the detection of recurrence and/or progression in the follow-up of non-muscle invasive BCa patients, and to assess the value of urinary biomarkers in predicting response to intravesical Bacillus Calmette–Guerin (BCG) therapy. Methods and materials A medline/pubmed© literature search was performed. The performance of commercially available and investigational biomarkers has been reviewed. End points were cancer detection (recurrence), cancer progression, and response to BCG therapy. Results The performance requirements for biomarkers are variable according to the clinical scenario. The clinical role of urinary biomarkers in the follow-up of non-muscle invasive BCa patients remains undefined. The FDA-approved tests provide unsatisfactory sensitivity and specificity levels and their use is limited. Fluorescence in situ hybridization (FISH) has been shown to be useful in specific scenarios, mostly as a reflex test and in the setting of equivocal urinary cytology. FISH and immunocytology could conceivably be used to assess BCG response. Recently developed biomarkers have shown promising results; upcoming large trials will test their utility in specific clinical scenarios in a manner similar to a phased drug development strategy. Conclusions Current commercially available urinary biomarker-based tests are not sufficiently validated to be widely used in clinical practice. Several novel biomarkers are currently under investigation. Prospective multicenter analyses will be needed to establish their clinical relevance and value.

                Author and article information

                Future Sci OA
                Future Sci OA
                Future Science OA
                Future Science Ltd (London, UK )
                11 October 2021
                October 2021
                11 October 2021
                : 7
                : 9
                : FSO758
                [1 ]Department of Oncology, University of Turin, Turin, Italy
                [2 ]Department of Surgical Sciences, University of Turin, Turin, Italy
                [3 ]Department of Medical Sciences, University of Turin, Turin, Italy
                [4 ]Department of Neurosciences, University of Turin, Turin, Italy
                [5 ]Division of Urology, Department of Surgical Sciences, AOU Città della Salute e della Scienza, Torino School of Medicine, Turin, Italy
                [6 ]SC Medical Genetics, AOU Città della Salute e della Scienza, Turin, Italy
                Author notes
                [* ]Author for correspondence: Tel.: +39 11 6705858; giuliana.giribaldi@ 123456unito.it

                Authors contributed equally

                Author information
                © 2021 The Authors

                This work is licensed under the Creative Commons Attribution 4.0 License

                : 05 May 2021
                : 30 August 2021
                : 11 October 2021
                Page count
                Pages: 10
                Research Article

                bladder cancer,fibrinogen β-chain,tyrosine-phosphorylated proteins,urinary markers


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