TY - JOUR
T1 - Transcriptome-wide signatures of tumor stage in kidney renal clear cell carcinoma
T2 - Connecting copy number variation, methylation and transcription factor activity
AU - Liu, Qi
AU - Su, Pei Fang
AU - Zhao, Shilin
AU - Shyr, Yu
N1 - Funding Information:
The authors wish to thank reviewers for valuable comments and Margot Bjoring for editorial work on this manuscript. This work was supported by National Cancer Institute grants U01 CA163056, P30 CA068485, P50 CA098131, and P50 CA090949 (to YS).
Publisher Copyright:
© 2014 Liu et al.
PY - 2014/12/11
Y1 - 2014/12/11
N2 - 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.
AB - 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.
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U2 - 10.1186/s13073-014-0117-z
DO - 10.1186/s13073-014-0117-z
M3 - Article
AN - SCOPUS:84927917742
VL - 6
JO - Genome Medicine
JF - Genome Medicine
SN - 1756-994X
IS - 12
M1 - 117
ER -