Transcriptome-wide signatures of tumor stage in kidney renal clear cell carcinoma: Connecting copy number variation, methylation and transcription factor activity

Qi Liu, Pei Fang Su, Shilin Zhao, Yu Shyr

研究成果: Article同行評審

7 引文 斯高帕斯(Scopus)

摘要

Background: Comparative analysis of expression profiles between early and late stage cancers can help to understand cancer progression and metastasis mechanisms and to predict the clinical aggressiveness of cancer. The observed stage-dependent expression changes can be explained by genetic and epigenetic alterations as well as transcription dysregulation. Unlike genetic and epigenetic alterations, however, activity changes of transcription factors, generally occurring at the post-transcriptional or post-translational level, are hard to detect and quantify.Methods: Here we developed a statistical framework to infer the activity changes of transcription factors by simultaneously taking into account the contributions of genetic and epigenetic alterations to mRNA expression variations.Results: Applied to kidney renal clear cell carcinoma (KIRC), the model underscored the role of methylation as a significant contributor to stage-dependent expression alterations and identified key transcription factors as potential drivers of cancer progression.Conclusions: Integrating copy number, methylation, and transcription factor activity signatures to explain stage-dependent expression alterations presented a precise and comprehensive view on the underlying mechanisms during KIRC progression.

原文English
文章編號117
期刊Genome Medicine
6
發行號12
DOIs
出版狀態Published - 2014 十二月 11

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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