Exploring the roles of urinary HAI-1, EpCAM &amp; EGFR in bladder cancer prognosis &amp; risk stratification

Snell, Kym I E; Ward, Douglas G.; Gordon, Naheema S.; Goldsmith, James; Sutton, Andrew; Patel, Prashant; James, Nicholas D.; Cheng, Kar Keung; Bryan, Richard T.

doi:10.18632/oncotarget.25397

Cited by 12 publications

(6 citation statements)

References 18 publications

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“…This highlights an important biological modification that would likely influence PD-L2 function. Such phenomena are well recognised in UBC and other malignancies (24). Further proteomic studies will be required to understand the cleavage and subsequent shedding of PD-L2 from the cell surface in advanced UBC.…”

Section: Discussionmentioning

confidence: 99%

PD-L2 Is Constitutively Expressed in Normal and Malignant Urothelium

et al. 2021

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The use of immune checkpoint blockade, in particular PD-1 and PD-L1 inhibitors, is now commonplace in many clinical settings including the treatment of muscle-invasive bladder cancer (MIBC). Notwithstanding, little information exists regarding the expression of the alternative PD-1 ligand, PD-L2 in urothelial bladder cancer (UBC). We therefore set out to characterise the expression of PD-L2 in comparison to PD-L1. Firstly, we assessed PD-L2 expression by immunohistochemistry and found widespread expression of PD-L2 in UBC, albeit with reduced expression in MIBC. We further investigated these findings using RNA-seq data from a cohort of 575 patients demonstrating that PDCD1LG2 (PD-L2) is widely expressed in UBC and correlated with CD274 (PD-L1). However, in contrast to our immunohistochemistry findings, expression was significantly increased in advanced disease. We have also provided detailed evidence of constitutive PD-L2 expression in normal urothelium and propose a mechanism by which PD-L2 is cleaved from the cell surface in MIBC. These data provide a comprehensive assessment of PD-L2 in UBC, showing PD-L2 is abundant in UBC and, importantly, constitutively present in normal urothelium. These data have implications for future development of immune checkpoint blockade, and also the understanding of the function of the immune system in the normal urinary bladder.

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Section: Discussionmentioning

confidence: 99%

PD-L2 Is Constitutively Expressed in Normal and Malignant Urothelium

et al. 2021

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“…Levels of CK20 and insulin-like growth factor II (IGF-II) were increased in the urine sediments of NMIBC patients compared to controls [ 73 ]. Increased urinary levels of HAI-1 and epithelial cell adhesion molecule (EpCAM) are prognostic biomarkers of high-risk in NMIBC patients [ 74 ]. Urinary survivin has been shown to be a potential biomarker for BC, and was further related to tumor stage, lymph node metastasis, and distant metastasis [ 75 ].…”

Section: Human Specimens-based Proteomics Biomarkersmentioning

confidence: 99%

“…Proteomics markers identified in different human samples are summarized in Table 4 [ 53 55 57 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 ].…”

Section: Human Specimens-based Proteomics Biomarkersmentioning

confidence: 99%

Proteomic profiling of bladder cancer for precision medicine in the clinical setting: A review for the busy urologist

et al. 2020

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At present, proteomic methods have successfully identified potential biomarkers of urological malignancies, such as prostate cancer (PC), bladder cancer (BC), and renal cell carcinoma (RCC), reflecting different numbers of key cellular processes, including extracellular environment modification, invasion and metastasis, chemotaxis, differentiation, metabolite transport, and apoptosis. The potential application of proteomics in the detection of clinical markers of urological malignancies can help improve patient assessment through early cancer detection, prognosis, and treatment response prediction. A variety of proteomic studies have already been carried out to find prognostic BC biomarkers, and a large number of potential biomarkers have been reported. It is worth noting that proteomics research has not been applied to the study of predictive markers; this may be due to the incompatibility between the number of measured variables and the available sample size, which has become particularly evident in the study of therapeutic response. On the contrary, prognostic correlation is more common, which is also reflected in existing research. We are now entering an era of clinical proteomics. Driven by proteomic-based workflows, computing tools, and the applicability of cross-correlation of proteomic data, it is now feasible to use proteomic analysis to support personalized medicine. In this paper, we will summarize the current emerging technologies for advanced discovery, targeted proteomics, and proteomic applications in BC, particularly in discovery of human-based biomarkers.

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“…Applications in disease prognosis have also been described, including the recent examples of the shed ectodomains of epithelial cell adhesion molecule (EpCAM) and hepatocyte growth factor activator inhibitor-1 (HA-1), exhibiting a prognostic value for disease-specific death (in the range of 2 times increased risk at increased marker levels) in NMIBC [77]; or various interleukins (such as IL12, TRAIL, TNFα) in response to BCG treatment [78].…”

Section: Protein Markersmentioning

confidence: 99%

Urinary-Based Markers for Bladder Cancer Detection

Todenhöfer¹,

Lodde²,

Kessel³

et al. 2020

Société Internationale D’Urologie Journal

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Background The use of urine markers for diagnosis and surveillance has been a topic of broad interest and ongoing controversies in the management of patients with bladder cancer. There has been a constant quest for markers that demonstrate clinical utility. Aim In the framework of the International Consultation on Urological Diseases 2019 on Molecular Biomarkers in Urologic Oncology, a comprehensive review of literature on urinary biomarkers for bladder cancer has been performed. Results Currently available urinary markers include protein-based markers, RNA-based markers, and DNA-based markers. The introduction of high-throughput analysis technologies provides the opportunity to assess multiple parameters within a short period of time, which is of interest for RNA-based, DNA-based, and protein-based marker systems. A comprehensive analysis of molecular alterations in urine samples of bladder cancer patients may be of interest not only for diagnosis and surveillance but also for non-invasive longitudinal assessment of molecular, potentially therapy-relevant, alterations. However, most systems lack prospective validation within well-designed trials and have not been broadly implemented in daily clinical practice. Conclusions Because of limited data from prospective trials, the routine use of any urine marker except cytology is not considered as standard of care in international guidelines. There is an urgent need for prospective trials of urine markers to answer specific clinical questions.

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Exploring the roles of urinary HAI-1, EpCAM & EGFR in bladder cancer prognosis & risk stratification

Cited by 12 publications

References 18 publications

PD-L2 Is Constitutively Expressed in Normal and Malignant Urothelium

PD-L2 Is Constitutively Expressed in Normal and Malignant Urothelium

Proteomic profiling of bladder cancer for precision medicine in the clinical setting: A review for the busy urologist

Urinary-Based Markers for Bladder Cancer Detection

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