Abstract
Simple SummaryAlthough immunohistochemistry is a routine technique in clinics, and genomics has been rapidly incorporated, proteomics is a step behind. This general situation is also the norm in bladder cancer research. This review shows the contributions of proteomics to the molecular classification of bladder cancer, and to the study of histopathology due to tissue insults caused by tumors. Furthermore, the importance of proteomics for understanding the cellular and molecular changes as a consequence of the therapy of bladder cancer cannot be neglected.Bladder cancer (BC) is the most common tumor of the urinary tract and is conventionally classified as either non-muscle invasive or muscle invasive. In addition, histological variants exist, as organized by the WHO-2016 classification. However, innovations in next-generation sequencing have led to molecular classifications of BC. These innovations have also allowed for the tracing of major tumorigenic pathways and, therefore, are positioned as strong supporters of precision medicine. In parallel, immunohistochemistry is still the clinical reference to discriminate histological layers and to stage BC. Key contributions have been made to enlarge the panel of protein immunomarkers. Moreover, the analysis of proteins in liquid biopsy has also provided potential markers. Notwithstanding, their clinical adoption is still low, with very few approved tests. In this context, mass spectrometry-based proteomics has remained a step behind; hence, we aimed to develop them in the community. Herein, the authors introduce the epidemiology and the conventional classifications to review the molecular classification of BC, highlighting the contributions of proteomics. Then, the advances in mass spectrometry techniques focusing on maintaining the integrity of the biological structures are presented, a milestone for the emergence of histoproteomics. Within this field, the review then discusses selected proteins for the comprehension of the pathophysiological mechanisms of BC. Finally, because there is still insufficient knowledge, this review considers proteomics as an important source for the development of BC therapies.
Highlights
All TCGA 2014 subtypes responded to the therapy, it was significantly higher in the luminal cluster II
This molecular classification of bladder cancer (BC) should enable the development of targeted therapies with properly designed clinical trials
Proteomics offers additional information on the behavior of the tumor, especially when we need to envisage the role of the immune system or tumor advancement through the different tissue layers
Summary
Histological staging of urothelial cancers is quite challenging, due to a high observer variability, but because two non-invasive types of lesions exist: papillary tumors (Ta), and carcinoma in situ (Tis) [9]. The initial stages of BC differ greatly at their genetic profile and clinical course levels; Hedegaard, J. et al proposed a three-way pathway to explain the progression from the Ta, Tis, and T1 NMIBC stages to MIBC [22] It can occur from either the Ta or the CIS (carcinoma in situ) pathway, the former being split into two subclasses, because the progression of one of the branches is firstly shifted towards CIS (Figure 2A). Mutations inhibiting the function of PTEN, which acts as a negative regulator, are common [37]; a reduced expression of PTEN—measured by immunohistochemistry—was associated with those BC patients who showed a higher progression and recurrence of their disease [38]
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