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. 2021 Jun 11;11:629860. doi: 10.3389/fonc.2021.629860

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Copyright © 2021 Huang, Fu, Zhang, Xu, Li, Onwuka, Zhang, Zhao, Sun, Zhu, Zheng, Jia, Cui and Zhao

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Mediation analysis for methylation-driven prognostic signature through mRNA expression. (A) Diagram of a mediation model. (B) The risk score of four methylation-driven genes’ methylation level was considered as “exposure” (score_methylation); the mediator was the linear combination of the corresponding four genes’ expression level (score_expression) (Overall model). Total prognostic effect in the hazard ratio (HR) was described as direct effect (HR_direct), indirect effect (HR_indirect), corresponding 95% CI, and the proportion of effect mediated (M%). Furthermore, sensitivity analyses were performed by excluding each gene, respectively, which retained statistical significance for the mediation effect. CI, confidence interval.