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Cancers 2019, 11(4), 501; https://doi.org/10.3390/cancers11040501

DNA Repair Gene Expression Adjusted by the PCNA Metagene Predicts Survival in Multiple Cancers

1
Department of Healthcare Policy and Research, Weill Cornell Medical College, Cornell University, New York City, NY 10065, USA
2
Center for Biostatistics, Institute for Academic Medicine, Houston Methodist Research Institute, 6565 Fannin Street, Houston, TX 77030, USA
*
Author to whom correspondence should be addressed.
Received: 3 February 2019 / Revised: 16 March 2019 / Accepted: 30 March 2019 / Published: 8 April 2019
PDF [743 KB, uploaded 8 April 2019]

Abstract

Removal of the proliferation component of gene expression by proliferating cell nuclear
antigen
(PCNA) adjustment via statistical methods has been addressed in numerous survival
prediction studies for breast cancer and all cancers in the Cancer Genome Atlas (TCGA). These
studies indicate that the removal of proliferation in gene expression by
PCNA adjustment removes
the statistical significance for predicting overall survival (OS) when gene selection is performed on
a genome-wide basis. Since cancers become addicted to DNA repair as a result of forced cellular
replication, increased oxidation, and repair deficiencies from oncogenic loss or genetic
polymorphisms, we hypothesized that
PCNA adjustment of DNA repair gene expression does not
remove statistical significance for OS prediction. The rationale and importance of this translational
hypothesis is that new lists of repair genes which are predictive of OS can be identified to establish
new targets for inhibition therapy. A candidate gene approach was employed using TCGA
RNA-Seq data for 121 DNA repair genes in 8 molecular pathways to predict OS for 18 cancers.
Statistical randomization test results indicate that after
PCNA adjustment, OS could be predicted
significantly by sets of DNA repair genes for 61% (11/18) of the cancers. These findings suggest that
removal of the proliferation signal in expression by
PCNA adjustment does not remove statistical
significance for predicting OS. In conclusion, it is likely that previous studies on
PCNA adjustment
and survival were biased because genes identified through a genome-wide approach are strongly
co-regulated by proliferation.
Keywords: RNA-seq; oncology; DNA repair; survival; PCNA metagene RNA-seq; oncology; DNA repair; survival; PCNA metagene
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Peterson, L.E.; Kovyrshina, T. DNA Repair Gene Expression Adjusted by the PCNA Metagene Predicts Survival in Multiple Cancers. Cancers 2019, 11, 501.

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