Loss of MTUS1/ATIP expression is associated with adverse outcome in advanced bladder carcinomas: data from a retrospective study

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• 作者：Anja Rogler (89)
  Sabine Hoja (89)
  Johannes Giedl (89)
  Arif B Ekici (90)
  Sven Wach (91)
  Helge Taubert (91)
  Peter J Goebell (91)
  Bernd Wullich (91)
  Michael St枚ckle (92)
  Jan Lehmann (93)
  Sabrina Petsch (94)
  Arndt Hartmann (89)
  Robert Stoehr (89)
  
  89. Institute of Pathology ; University Hospital Erlangen ; Krankenhausstr. 8-10 ; 91054 ; Erlangen ; Germany
  90. Institute of Human Genetics ; Friedrich-Alexander Universit盲t Erlangen-N眉rnberg ; Schwabachanlage 10 ; 91054 ; Erlangen ; Germany
  91. Department of Urology ; University Hospital Erlangen ; Krankenhausstr. 12 ; 91054 ; Erlangen ; Germany
  92. Clinic for Urology and Children鈥檚 Urology ; University Hospital Saarland ; Kirrberger Strasse ; 66421 ; Homburg/Saar ; Germany
  93. Urology Practice Pr眉ner Gang ; Pr眉ner Gang 15 ; 24105 ; Kiel ; Germany
  94. Tumour Zentrum ; Friedrich-Alexander Universit盲t Erlangen-N眉rnberg ; Carl-Thiersch-Str. 7 ; 91052 ; Erlangen ; Germany
  
• 关键词：MTUS1 ; ATIP ; Bladder cancer ; Chromosome 8p deletions
• 刊名：BMC Cancer
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：14
• 期：1
• 全文大小：928 KB
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  39. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/14/214/prepub
  
• 刊物主题：Cancer Research; Oncology; Stem Cells; Animal Models; Internal Medicine;
• 出版者：BioMed Central
• ISSN：1471-2407

文摘

Background Seventy percent of all bladder tumours tend to recur and need intensive surveillance, and a subset of tumours progress to muscle-invasive and metastatic disease. However, it is still difficult to find the adequate treatment for every individual patient as it is a very heterogeneous disease and reliable biomarkers are still missing. In our study we searched for new target genes in the critical chromosomal region 8p and investigated the potential tumour suppressor gene candidate MTUS1/ATIP in bladder cancer. Methods MTUS1 was identified to be the most promising deleted target gene at 8p in aCGH analysis with 19 papillary bladder tumours. A correlation with bladder cancer was further validated using immunohistochemistry of 85 papillary and 236 advanced bladder tumours and in functional experiments. Kaplan-Meier analysis and multivariate Cox-regression addressed overall survival (OS) and disease-specific survival (DSS) as a function of MTUS1/ATIP expression. Bivariate correlations investigated associations between MTUS1/ATIP expression, patient characteristics and histopathology. MTUS1 expression was analysed in cell lines and overexpressed in RT112, where impact on viability, proliferation and migration was measured. Results MTUS1 protein expression was lost in almost 50% of all papillary and advanced bladder cancers. Survival, however, was only influenced in advanced carcinomas, where loss of MTUS1 was associated with adverse OS and DSS. In this cohort, there was also a significant correlation of MTUS1 expression and histological subtype: positive expression was detected in all micropapillary tumours and aberrant nuclear staining was detected in a subset of plasmocytoid urothelial carcinomas. MTUS1 was expressed in all investigated bladder cell lines and overexpression in RT112 led to significantly decreased viability. Conclusions MTUS1 is a tumour suppressor gene in cultured bladder cancer cells and in advanced bladder tumours. It might represent one new target gene at chromosome 8p and can be used as an independent prognostic factor for advanced bladder cancer patients. The limitation of the study is the retrospective data analysis. Thus, findings should be validated with a prospective advanced bladder tumour cohort.