Global gene expression profiling identifies ALDH2, CCNE1 and SMAD3 as potential prognostic markers in upper tract urothelial carcinoma

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• 作者：Song Wu (1) (2) (3) (4)
  Jiahao Chen (5) (9)
  Pei Dong (3)
  Shiqiang Zhang (2)
  Yingying He (6)
  Liang Sun (2)
  Jialou Zhu (5)
  Yanbing Cheng (5)
  Xianxin Li (6)
  Aifa Tang (2)
  Yi Huang (2)
  Yaoting Gui (6)
  Chunxiao Liu (7)
  Guosheng Yang (8)
  Fangjian Zhou (3)
  Zhiming Cai (2) (4)
  Rongfu Wang (1)
  
  1. Institute of Immunology ; Zhongshan School of Medicine ; Sun Yat-sen University ; Guangzhou ; Guangdong ; 510060 ; China
  2. Shenzhen Second People鈥檚 Hospital ; The First Affiliated Hospital of Shenzhen University ; Shenzhen ; Guangdong ; 518035 ; China
  3. Department of Urology ; Sun Yat-Sen University Cancer Center ; Guangzhou ; Guangdong ; 510060 ; China
  4. National-regional Key Technology Engineering Laboratory for Clinical Application of Cancer Genomics ; Shenzhen Key Laboratory of Genitourinary Tumor ; Shenzhen ; Guangdong ; 518036 ; China
  5. BGI-Shenzhen ; Shenzhen ; Guangdong ; 518083 ; China
  9. Department of Cell Biology ; Albert Einstein College of Medicine ; Bronx ; NY ; 10461 ; USA
  6. Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics ; Institute of Urology ; Peking University Shenzhen Hospital ; Shenzhen PKU-HKUST Medical Center ; Shenzhen ; Guangdong ; 518036 ; China
  7. Department of Urology ; Zhujiang Hospital ; Southern Medical University ; Guangzhou ; 510282 ; China
  8. Department of Urology ; Guangzhou Second People鈥檚 Hospital ; Guangzhou ; Guangdong ; 510282 ; China
  
• 关键词：Upper tract urothelial carcinoma of renal pelvis ; Global gene expression profiling ; ALDH2 ; CCNE1 ; SMAD3 ; Prognosis
• 刊名：BMC Cancer
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：14
• 期：1
• 全文大小：1,191 KB
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  39. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/14/836/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 Current knowledge about the molecular properties and prognostic markers of upper tract urothelial carcinoma (UTUC) is sparse and often based on bladder urothelial carcinoma (UC), which is thought to share common risk factors with UTUC. However, studies have suggested that differences exist regarding tumor behavior and molecular biology of these cancers, comprehensive investigations are needed to guide the clinical management of UTUC. In recent years, massively parallel sequencing has allowed insights into the biology of many cancers, and molecular prognostic markers based on this approach are rapidly emerging. The goal of this study was to characterize the gene expression patterns of UTUC using massively parallel sequencing, and identify potential molecular markers for prognosis in patients with UTUC. Methods We compared the genome-wide mRNA expression profile of cancer and matched normal tissues from 10 patients with UTUC to identify significantly deregulated genes. We also examined the protein levels of prognostic marker candidates in 103 patients with UTUC, and tested the association of these markers with overall survival using Kaplan-Meier model and Cox regression. Results Functional enrichment of significantly deregulated genes revealed that expression patterns of UTUC were characterized by disorders of cell proliferation and metabolism. And we also compared the expression profile of UTUC with that of bladder UC. Our results highlighted both shared (e.g. disorders of cell cycling and growth signal transduction) and tumor-specific (e.g. abnormal metabolism in UTUC and disruptions of adhesion pathways in bladder UC) features of these two cancers. Importantly, we identified that low protein expression of ALDH2 while high CCNE1 and SMAD3 were significantly associated with increased depth (*P Conclusions In conclusion, our study characterized the comprehensive expression profile of UTUC and highlighted both commons and differences in expression patterns between UTUC and bladder UC. And we, for the first time, revealed that ALDH2, CCNE1 and SMAD3 are associated with prognosis in patients with UTUC.