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. 2020 Apr 2;3:158. doi: 10.1038/s42003-020-0873-9

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© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 3 — a MCF7 cells and isogenic RB1 deleted model were treated with CDK4/6 inhibitor (250 nM palbociclib) for 48 h. RNA sequencing was used to define transcriptional repression events that are RB dependent thereby linking CDK4/6 inhibition to RB-activation. b The CDK4/6-RB integrated signature was applied to data from the NeoPalaAnna trial and exhibited consistent repression in this clinical cohort of tumors treated with CDK4/6 inhibitors (pre-treatment N = 32, on treatment N = 28). Box plot shows difference in the integrated signature between pre and on-treatment samples (Student’s t-test two sided: ****p < 0.0001) c Heatmaps illustrate that general behavior of the CDK4/6-RB integrated signature across several tumors types. d Kaplan–Meier analysis of the indicated tumor types stratified by CDK4/6-RB integrated signature. Disease-free survival is shown, and statistical analysis is by log-rank approach. e Pan-cancer relationship of the CDK4/6-RB integrated signature expression value. Color bar indicates tumors wherein high levels of the CDK4/6-RB integrated signature (indicative of high CDK4/6 activity or RB loss) are significantly associated with poor prognosis (blue) or not (red). f Relative expression of the CDK4/6-RB integrated signature in luminal (N = 1175) vs. basal (N = 209) breast cancer subtypes in the METABRIC data set (Student’s t-test two side: p < 0.001). Kaplan–Meier analysis of luminal and basal breast cancer stratified by the CDK4/6-RB integrated signature. Statistical analysis is by log-rank approach.