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. 2022 May 12;13:2642. doi: 10.1038/s41467-022-30375-8

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© The Author(s) 2022

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. 8 — a Pearson correlation coefficient analysis of the METABRIC breast cancer patient cohort showing positive correlation of a SGOC network gene signature (SGOC_CDK12 average z-score) with CDK12 transcript levels (CDK12 z-score) in all breast cancers and in the indicated molecular subtypes. Derivation of the SGOC_CDK12 signature is described in Supplementary Fig. 4. The number of patients in each group is indicated. R, correlation coefficient value; P, P-value. Padj, FDR adjusted P value for the 3 subgroups tested. b Cumulative incidence of distant metastasis in CDK12^HIGH, CDK12^LOW and CDK12^NULL HER2-negative (HER2-neg) breast cancer patients in response to chemotherapy (CT) with taxane/anthracycline (Tax/AC)- vs. methotrexate-based (CMF, cyclophosphamide, MTX, fluorouracil). The 10-year cumulative distant metastasis rate (%) and the patient number of each class are indicated. HR, multivariable hazard ratio adjusted for standard clinical parameters (see Methods). P, P-value, stratified Wald test. c Cumulative distant metastasis in CDK12^HIGH and CDK12^LOW hormone-negative, lymph node-positive patients randomized to metronomic cyclophosphamide+methotrexate (CM) chemotherapy vs. no chemotherapy (control, Ctr). Patients no.: CDK12^HIGH = 31, CDK12^LOW = 73 in the control group; CDK12^HIGH = 35, CDK12^LOW = 74 in the CM therapy group. HR, hazard ratio (see also Supplementary Fig. 5c for cohort description and multivariable analyses). P, P-value, stratified likelihood-ratio test. d Cumulative incidence of deaths in CDK12^HIGH vs. CDK12^LOW neoadjuvant triple-negative breast cancer (TNBC) patients treated with second-line CMF after failure of first-line Tax/AC chemotherapy. HR, multivariable hazard ratio for CDK12^HIGH vs. CDK12^LOW patients. The 10-year cumulative death rate (%) for each category is indicated. Patient no., CDK12^HIGH = 82, CDK12^LOW = 43, see also Supplementary Fig. 5e). HR, multivariable hazard ratio; P, P-value, stratified Wald test. Source data are provided as Source Data file.