Department of Public Health, Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
Bioinformatics and Biostatistics Core, Center of Genomic and Precision Medicine, National Taiwan University, Taipei, Taiwan.
J Adv Res. 2020 Nov 11;30:113-122. doi: 10.1016/j.jare.2020.11.006. eCollection 2021 May.
Ovarian cancer (OC) is one of the most frequent gynecologic cancers among women, and high-accuracy risk prediction techniques are essential to effectively select the best intervention strategies and clinical management for OC patients at different risk levels. Current risk prediction models used in OC have low sensitivity, and few of them are able to identify OC patients at high risk of mortality, which would both optimize the treatment of high-risk patients and prevent unnecessary medical intervention in those at low risk.
To this end, we have developed a bagging-based algorithm with GA-XGBoost models that predicts the risk of death from OC using gene expression profiles.
Four gene expression datasets from public sources were used as training (n = 1) or validation (n = 3) sets. The performance of our proposed algorithm was compared with fine-tuning and other existing methods. Moreover, the biological function of selected genetic features was further interpreted, and the response to a panel of approved drugs was predicted for different risk levels.
The proposed algorithm showed good sensitivity (74-100%) in the validation sets, compared with two simple models whose sensitivity only reached 47% and 60%. The prognostic gene signature used in this study was highly connected to , a key component of the PI3K/AKT/mTOR signaling pathway, which influences the tumorigenesis, proliferation, and progression of OC.
These findings demonstrated an improvement in the sensitivity of risk classification of OC patients with our risk prediction models compared with other methods. Ongoing effort is needed to validate the outcomes of this approach for precise clinical treatment.
卵巢癌(OC)是女性最常见的妇科癌症之一,因此需要高精度的风险预测技术,以便为不同风险水平的 OC 患者有效选择最佳干预策略和临床管理。目前 OC 中使用的风险预测模型灵敏度较低,而且很少有模型能够识别 OC 患者的高死亡率风险,这将优化高危患者的治疗,并防止低风险患者进行不必要的医疗干预。
为此,我们开发了一种基于 bagging 的算法,结合 GA-XGBoost 模型,使用基因表达谱预测 OC 死亡风险。
从公共资源中使用了四个基因表达数据集作为训练(n=1)或验证(n=3)集。将我们提出的算法的性能与微调及其他现有方法进行了比较。此外,还进一步解释了选定遗传特征的生物学功能,并预测了不同风险水平下对一组批准药物的反应。
与灵敏度仅达到 47%和 60%的两个简单模型相比,所提出的算法在验证集中显示出良好的灵敏度(74%-100%)。本研究中使用的预后基因特征与 PI3K/AKT/mTOR 信号通路的关键组成部分,即 高度相关,它影响 OC 的肿瘤发生、增殖和进展。
与其他方法相比,我们的风险预测模型提高了 OC 患者风险分类的灵敏度。需要进一步努力验证这种方法在精确临床治疗中的结果。