Abstract

Bladder cancer represents the ninth most widespread malignancy throughout the world. It is characterized by the presence of two different clinical and prognostic subtypes: non-muscle-invasive bladder cancers (NMIBCs) and muscle-invasive bladder cancers (MIBCs). MIBCs have a poor outcome with a common progression to metastasis. Despite improvements in knowledge, treatment has not advanced significantly in recent years, with the absence of new therapeutic targets. Because of the limitations of current therapeutic options, the greater challenge will be to identify biomarkers for clinical application. For this reason, we compared our array comparative genomic hybridization (array-CGH) results with those reported in literature for invasive bladder tumors and, in particular, we focused on the evaluation of copy number alterations (CNAs) present in biopsies and retained in the corresponding cancer stem cell (CSC) subpopulations that should be the main target of therapy. According to our data, CCNE1, MYC, MDM2 and PPARG genes could be interesting therapeutic targets for bladder CSC subpopulations. Surprisingly, HER2 copy number gains are not retained in bladder CSCs, making the gene-targeted therapy less interesting than the others. These results provide precious advice for further study on bladder therapy; however, the clinical importance of these results should be explored.

Highlights

  • Bladder cancer represents the ninth most widespread malignancy with 429,000 new cases and about 165,000 fatalities in 2012 (2% of the total number of cancer deaths)

  • We compared our array-comparative genomic hybridization copy number alterations (CNAs) (CGH) results with those reported in literature for invasive bladder tumors (Table 1); in particular, we focused on the comparison of selected genes identified by the Cancer Genome Atlas analysis [10,11] to be the most significant in this type of tumor

  • Our approach could lead to detecting potential therapeutic targets through the evaluation of copy number alterations (CNAs) both in biopsies and in the corresponding isolated cancer stem cell (CSC) subpopulations

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Summary

Introduction

Bladder cancer represents the ninth most widespread malignancy with 429,000 new cases and about 165,000 fatalities in 2012 (2% of the total number of cancer deaths). It occurs in men more than in women, with a sex ratio of 3.5 [1]. More than 90% of these tumors are transitional cell carcinomas (TCC, urothelial carcinoma) This tumor is characterized by the presence of two different clinical and prognostic subtypes: non-muscle-invasive bladder cancers (NMIBCs) and muscle-invasive bladder cancers (MIBCs). About 20% of cancers present muscle invasion at diagnosis, an unfavorable outcome with a survival rate after five years below 50% [3] and common progression to metastasis

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