|Global gene expression profiling identifies ALDH2, CCNE1 and SMAD3 as potential prognostic markers in upper tract urothelial carcinoma|
|Wu, Song1,2,3,4; Chen, Jiahao5; Dong, Pei3; Zhang, Shiqiang2; He, Yingying6; Sun, Liang2; Zhu, Jialou1; Cheng, Yanbing5; Li, Xianxin6; Tang, Aifa2; Huang, Yi2; Gui, Yaoting6; Liu, Chunxiao7; Yang, Guosheng8; Zhou, Fangjian3; Cai, Zhiming2,4; Wang, Rongfu1|
|关键词||Upper Tract Urothelial Carcinoma Of Renal Pelvis Global Gene Expression Profiling Aldh2 Ccne1 Smad3 Prognosis|
|WOS标题词||Science & Technology|
|关键词[WOS]||TRANSITIONAL-CELL CARCINOMA ; UPPER URINARY-TRACT ; DISTINCT PATTERNS ; PROSTATE-CANCER ; BREAST-CANCER ; KIDNEY CANCER ; TUMORS ; PROGRESSION ; PREDICTORS ; CYTOSCAPE|
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 < 0.05) and lower overall survival (***P < 0.0001) in an independent set of 103 patients. Multivariate Cox regression revealed that all these three genes were independent prognostic indicators in patients with UTUC (***P < 0.001).
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.
|项目编号||81301740 ; 201001Y0104687244 ; JCYJ20130401114928183 ; JCYJ20130401114715714 ; JSGG20130411091246833|
|资助机构||National Natural Science Foundation ; Guangdong Innovative R& ; D Team Foundation ; Shenzhen Basic Research Project ; Shenzhen Knowledge Innovation Project ; Shenzhen technological breakthrough project of China|
|作者单位||1.Sun Yat Sen Univ, Zhongshan Sch Med, Inst Immunol, Guangzhou 510060, Guangdong, Peoples R China|
2.Shenzhen Univ, Affiliated Hosp 1, Shenzhen Peoples Hosp 2, Shenzhen 518035, Guangdong, Peoples R China
3.Sun Yat Sen Univ, Ctr Canc, Dept Urol, Guangzhou 510060, Guangdong, Peoples R China
4.Shenzhen Key Lab Genitourinary Tumor, Natl Reg Key Technol Engn Lab Clin Applicat Canc, Shenzhen 518036, Guangdong, Peoples R China
5.BGI Shenzhen, Shenzhen 518083, Guangdong, Peoples R China
6.Peking Univ, Shenzhen PKU HKUST Med Ctr, Inst Urol,Shenzhen Hosp, Guangdong & Shenzhen Key Lab Male Reprod Med & G, Shenzhen 518036, Guangdong, Peoples R China
7.Southern Med Univ, Zhujiang Hosp, Dept Urol, Guangzhou 510282, Guangdong, Peoples R China
8.Guangzhou Second Peoples Hosp, Dept Urol, Guangzhou 510282, Guangdong, Peoples R China
|Wu, Song,Chen, Jiahao,Dong, Pei,et al. Global gene expression profiling identifies ALDH2, CCNE1 and SMAD3 as potential prognostic markers in upper tract urothelial carcinoma[J]. BMC CANCER,2014,14.|
|APA||Wu, Song.,Chen, Jiahao.,Dong, Pei.,Zhang, Shiqiang.,He, Yingying.,...&Wang, Rongfu.(2014).Global gene expression profiling identifies ALDH2, CCNE1 and SMAD3 as potential prognostic markers in upper tract urothelial carcinoma.BMC CANCER,14.|
|MLA||Wu, Song,et al."Global gene expression profiling identifies ALDH2, CCNE1 and SMAD3 as potential prognostic markers in upper tract urothelial carcinoma".BMC CANCER 14(2014).|