1. Global gene expression profiling identifies ALDH2, CCNE1 and SMAD3 as potential prognostic markers in upper tract urothelial carcinoma
- Author
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Yaoting Gui, Pei Dong, Guosheng Yang, Yingying He, Jialou Zhu, Fangjian Zhou, Liang Sun, Yi Huang, Yanbing Cheng, Rongfu Wang, Jiahao Chen, Song Wu, Aifa Tang, Shiqiang Zhang, Chunxiao Liu, Zhiming Cai, and Xianxin Li
- Subjects
Adult ,Male ,Urologic Neoplasms ,Cancer Research ,Low protein ,Biology ,Upper tract urothelial carcinoma of renal pelvis ,SMAD3 ,Surgical oncology ,Cyclin E ,Biomarkers, Tumor ,Genetics ,medicine ,Cluster Analysis ,Humans ,Gene Regulatory Networks ,Kidney Pelvis ,Smad3 Protein ,ALDH2 ,Aged ,Neoplasm Staging ,Aged, 80 and over ,Oncogene Proteins ,Regulation of gene expression ,Massive parallel sequencing ,Proportional hazards model ,Aldehyde Dehydrogenase, Mitochondrial ,Gene Expression Profiling ,Reproducibility of Results ,Cancer ,Aldehyde Dehydrogenase ,Middle Aged ,CCNE1 ,Prognosis ,medicine.disease ,Immunohistochemistry ,Kidney Neoplasms ,Gene Expression Regulation, Neoplastic ,Gene expression profiling ,Urinary Bladder Neoplasms ,Oncology ,Cancer research ,Global gene expression profiling ,Female ,Research Article - Abstract
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
- Published
- 2014
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