Maojie Xue, Ziang Xu, Xiang Wang, Jiajin Chen, Xinxin Kong, Shenxuan Zhou, Jiamin Wu, Yuhao Zhang, Yi Li, David C Christiani, Feng Chen, Yang Zhao, Ruyang Zhang
{"title":"ARTEMIS：经独立验证的乳腺癌预后预测模型，其中包含具有主效应和基因-基因相互作用的表观遗传生物标志物。","authors":"Maojie Xue, Ziang Xu, Xiang Wang, Jiajin Chen, Xinxin Kong, Shenxuan Zhou, Jiamin Wu, Yuhao Zhang, Yi Li, David C Christiani, Feng Chen, Yang Zhao, Ruyang Zhang","doi":"10.1016/j.jare.2024.08.015","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Breast cancer, a heterogeneous disease, is influenced by multiple genetic and epigenetic factors. The majority of prognostic models for breast cancer focus merely on the main effects of predictors, disregarding the crucial impacts of gene-gene interactions on prognosis.</p><p><strong>Objectives: </strong>Using DNA methylation data derived from nine independent breast cancer cohorts, we developed an independently validated prognostic prediction model of breast cancer incorporating epigenetic biomarkers with main effects and gene-gene interactions (ARTEMIS) with an innovative 3-D modeling strategy. ARTEMIS was evaluated for discrimination ability using area under the receiver operating characteristics curve (AUC), and calibration using expected and observed (E/O) ratio. Additionally, we conducted decision curve analysis to evaluate its clinical efficacy by net benefit (NB) and net reduction (NR). Furthermore, we conducted a systematic review to compare its performance with existing models.</p><p><strong>Results: </strong>ARTEMIS exhibited excellent risk stratification ability in identifying patients at high risk of mortality. Compared to those below the 25th percentile of ARTEMIS scores, patients with above the 90th percentile had significantly lower overall survival time (HR = 15.43, 95% CI: 9.57-24.88, P = 3.06 × 10<sup>-29</sup>). ARTEMIS demonstrated satisfactory discrimination ability across four independent populations, with pooled AUC<sub>3-year</sub> = 0.844 (95% CI: 0.805-0.883), AUC<sub>5-year</sub> = 0.816 (95% CI: 0.775-0.857), and C-index = 0.803 (95% CI: 0.776-0.830). Meanwhile, ARTEMIS had well calibration performance with pooled E/O ratio 1.060 (95% CI: 1.038-1.083) and 1.090 (95% CI: 1.057-1.122) for 3- and 5-year survival prediction, respectively. Additionally, ARTEMIS is a clinical instrument with acceptable cost-effectiveness for detecting breast cancer patients at high risk of mortality (P<sub>t</sub> = 0.4: NB<sub>3-year</sub> = 19‰, NB<sub>5-year</sub> = 62‰; NR<sub>3-year</sub> = 69.21%, NR<sub>5-year</sub> = 56.01%). ARTEMIS has superior performance compared to existing models in terms of accuracy, extrapolation, and sample size, as indicated by the systematic review. ARTEMIS is implemented as an interactive online tool available at http://bigdata.njmu.edu.cn/ARTEMIS/.</p><p><strong>Conclusion: </strong>ARTEMIS is an efficient and practical tool for breast cancer prognostic prediction.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"ARTEMIS: An independently validated prognostic prediction model of breast cancer incorporating epigenetic biomarkers with main effects and gene-gene interactions.\",\"authors\":\"Maojie Xue, Ziang Xu, Xiang Wang, Jiajin Chen, Xinxin Kong, Shenxuan Zhou, Jiamin Wu, Yuhao Zhang, Yi Li, David C Christiani, Feng Chen, Yang Zhao, Ruyang Zhang\",\"doi\":\"10.1016/j.jare.2024.08.015\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Breast cancer, a heterogeneous disease, is influenced by multiple genetic and epigenetic factors. The majority of prognostic models for breast cancer focus merely on the main effects of predictors, disregarding the crucial impacts of gene-gene interactions on prognosis.</p><p><strong>Objectives: </strong>Using DNA methylation data derived from nine independent breast cancer cohorts, we developed an independently validated prognostic prediction model of breast cancer incorporating epigenetic biomarkers with main effects and gene-gene interactions (ARTEMIS) with an innovative 3-D modeling strategy. ARTEMIS was evaluated for discrimination ability using area under the receiver operating characteristics curve (AUC), and calibration using expected and observed (E/O) ratio. Additionally, we conducted decision curve analysis to evaluate its clinical efficacy by net benefit (NB) and net reduction (NR). Furthermore, we conducted a systematic review to compare its performance with existing models.</p><p><strong>Results: </strong>ARTEMIS exhibited excellent risk stratification ability in identifying patients at high risk of mortality. Compared to those below the 25th percentile of ARTEMIS scores, patients with above the 90th percentile had significantly lower overall survival time (HR = 15.43, 95% CI: 9.57-24.88, P = 3.06 × 10<sup>-29</sup>). ARTEMIS demonstrated satisfactory discrimination ability across four independent populations, with pooled AUC<sub>3-year</sub> = 0.844 (95% CI: 0.805-0.883), AUC<sub>5-year</sub> = 0.816 (95% CI: 0.775-0.857), and C-index = 0.803 (95% CI: 0.776-0.830). Meanwhile, ARTEMIS had well calibration performance with pooled E/O ratio 1.060 (95% CI: 1.038-1.083) and 1.090 (95% CI: 1.057-1.122) for 3- and 5-year survival prediction, respectively. Additionally, ARTEMIS is a clinical instrument with acceptable cost-effectiveness for detecting breast cancer patients at high risk of mortality (P<sub>t</sub> = 0.4: NB<sub>3-year</sub> = 19‰, NB<sub>5-year</sub> = 62‰; NR<sub>3-year</sub> = 69.21%, NR<sub>5-year</sub> = 56.01%). ARTEMIS has superior performance compared to existing models in terms of accuracy, extrapolation, and sample size, as indicated by the systematic review. ARTEMIS is implemented as an interactive online tool available at http://bigdata.njmu.edu.cn/ARTEMIS/.</p><p><strong>Conclusion: </strong>ARTEMIS is an efficient and practical tool for breast cancer prognostic prediction.</p>\",\"PeriodicalId\":94063,\"journal\":{\"name\":\"Journal of advanced research\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-08-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of advanced research\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jare.2024.08.015\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of advanced research","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.jare.2024.08.015","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
ARTEMIS: An independently validated prognostic prediction model of breast cancer incorporating epigenetic biomarkers with main effects and gene-gene interactions.
Introduction: Breast cancer, a heterogeneous disease, is influenced by multiple genetic and epigenetic factors. The majority of prognostic models for breast cancer focus merely on the main effects of predictors, disregarding the crucial impacts of gene-gene interactions on prognosis.
Objectives: Using DNA methylation data derived from nine independent breast cancer cohorts, we developed an independently validated prognostic prediction model of breast cancer incorporating epigenetic biomarkers with main effects and gene-gene interactions (ARTEMIS) with an innovative 3-D modeling strategy. ARTEMIS was evaluated for discrimination ability using area under the receiver operating characteristics curve (AUC), and calibration using expected and observed (E/O) ratio. Additionally, we conducted decision curve analysis to evaluate its clinical efficacy by net benefit (NB) and net reduction (NR). Furthermore, we conducted a systematic review to compare its performance with existing models.
Results: ARTEMIS exhibited excellent risk stratification ability in identifying patients at high risk of mortality. Compared to those below the 25th percentile of ARTEMIS scores, patients with above the 90th percentile had significantly lower overall survival time (HR = 15.43, 95% CI: 9.57-24.88, P = 3.06 × 10-29). ARTEMIS demonstrated satisfactory discrimination ability across four independent populations, with pooled AUC3-year = 0.844 (95% CI: 0.805-0.883), AUC5-year = 0.816 (95% CI: 0.775-0.857), and C-index = 0.803 (95% CI: 0.776-0.830). Meanwhile, ARTEMIS had well calibration performance with pooled E/O ratio 1.060 (95% CI: 1.038-1.083) and 1.090 (95% CI: 1.057-1.122) for 3- and 5-year survival prediction, respectively. Additionally, ARTEMIS is a clinical instrument with acceptable cost-effectiveness for detecting breast cancer patients at high risk of mortality (Pt = 0.4: NB3-year = 19‰, NB5-year = 62‰; NR3-year = 69.21%, NR5-year = 56.01%). ARTEMIS has superior performance compared to existing models in terms of accuracy, extrapolation, and sample size, as indicated by the systematic review. ARTEMIS is implemented as an interactive online tool available at http://bigdata.njmu.edu.cn/ARTEMIS/.
Conclusion: ARTEMIS is an efficient and practical tool for breast cancer prognostic prediction.
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