Integrated transcriptional profiling and genomic analyses reveal RPN2 and HMGB1 as promising biomarkers in colorectal cancer

	Integrated transcriptional profiling and genomic analyses reveal RPN2 and HMGB1 as promising biomarkers in colorectal cancer
	Jialing Zhang; Bin Yan; Stephan Stanislaw Späth; Hu Qun; Shaleeka Cornelius; Daogang Guan; Jiaofang Shao; Koichi Hagiwara; Carter Van Waes; Zhong Chen
刊名	CELL AND BIOSCIENCE
	2015
英文摘要	Colorectal cancer (CRC) is a heterogeneous disease that is associated with a gradual accumulation of genetic and epigenetic alterations. Among all CRC stages, stage II tumors are highly heterogeneous with a high relapse rate in about 20-25 % of stage II CRC patients following surgery. Thus, a comprehensive analysis of gene signatures to identify aggressive and metastatic phenotypes in stage II CRC is desired for a more accurate disease classification and outcome prediction. By utilizing a Cancer Array, containing 440 oncogenes and tumor suppressors to profile mRNA expression, we identified a larger number of differentially expressed genes in poorly differentiated stage II colorectal adenocarcinoma tissues, compared to their matched normal tissues. Ontology and Ingenuity Pathway Analysis (IPA) indicated that these genes are involved in functional mechanisms associated with several transcription factors. Genomic alterations of these genes were also investigated through The Cancer Genome Atlas (TCGA) database, utilizing 195 published CRC specimens. The percentage of genomic alterations in these genes was ranked based on their mRNA expression, copy number variations and mutations. This data was further combined with published microarray studies from a large set of CRC tumors classified based on prognostic features. This led to the identification of eight candidate genes including RPN2, HMGB1, AARS, IGFBP3, STAT1, HYOU1, NQO1 and PEA15 that were associated with the progressive phenotype. In particular, RPN2 and HMGB1 displayed a higher genomic alteration frequency in CRC, compared to eight other major solid cancers. Immunohistochemistry was performed on additional 78 stage I-IV CRC samples, where RPN2 protein immunostaining exhibited a significant association with stage III/IV tumors, distant metastasis, and poor differentiation, indicating that RPN2 expression is associated with poor prognosis. Further, our study revealed significant transcriptional regulatory mechanisms, networks and gene signatures, underlying CRC malignant progression and phenotype warranting future clinical investigations.
收录类别	SCI
原文出处	http://cellandbioscience.biomedcentral.com/articles/10.1186/s13578-015-0043-9
语种	英语
内容类型	期刊论文
源URL	[http://ir.siat.ac.cn:8080/handle/172644/7406]
专题	深圳先进技术研究院_医药所
作者单位	CELL AND BIOSCIENCE
推荐引用方式 GB/T 7714	Jialing Zhang,Bin Yan,Stephan Stanislaw Späth,et al. Integrated transcriptional profiling and genomic analyses reveal RPN2 and HMGB1 as promising biomarkers in colorectal cancer[J]. CELL AND BIOSCIENCE,2015.
APA	Jialing Zhang.,Bin Yan.,Stephan Stanislaw Späth.,Hu Qun.,Shaleeka Cornelius.,...&Yongyi Bi.(2015).Integrated transcriptional profiling and genomic analyses reveal RPN2 and HMGB1 as promising biomarkers in colorectal cancer.CELL AND BIOSCIENCE.
MLA	Jialing Zhang,et al."Integrated transcriptional profiling and genomic analyses reveal RPN2 and HMGB1 as promising biomarkers in colorectal cancer".CELL AND BIOSCIENCE (2015).