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基于上皮-间质转化相关基因的机器学习和多组学方法构建结直肠癌个体化预后风险模型。

Constructing a personalized prognostic risk model for colorectal cancer using machine learning and multi-omics approach based on epithelial-mesenchymal transition-related genes.

机构信息

Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, China.

出版信息

J Gene Med. 2024 Jan;26(1):e3660. doi: 10.1002/jgm.3660.

Abstract

The progression and the metastatic potential of colorectal cancer (CRC) are intricately linked to the epithelial-mesenchymal transition (EMT) process. The present study harnesses the power of machine learning combined with multi-omics data to develop a risk stratification model anchored on EMT-associated genes. The aim is to facilitate personalized prognostic assessments in CRC. We utilized publicly accessible gene expression datasets to pinpoint EMT-associated genes, employing a CoxBoost algorithm to sift through these genes for prognostic significance. The resultant model, predicated on gene expression levels, underwent rigorous independent validation across various datasets. Our model demonstrated a robust capacity to segregate CRC patients into distinct high- and low-risk categories, each correlating with markedly different survival probabilities. Notably, the risk score emerged as an independent prognostic indicator for CRC. High-risk patients were characterized by an immunosuppressive tumor milieu and a heightened responsiveness to certain chemotherapeutic agents, underlining the model's potential in steering tailored oncological therapies. Moreover, our research unearthed a putative repressive interaction between the long non-coding RNA PVT1 and the EMT-associated genes TIMP1 and MMP1, offering new insights into the molecular intricacies of CRC. In essence, our research introduces a sophisticated risk model, leveraging machine learning and multi-omics insights, which accurately prognosticates outcomes for CRC patients, paving the way for more individualized and effective oncological treatment paradigms.

摘要

结直肠癌(CRC)的进展和转移潜能与上皮-间充质转化(EMT)过程密切相关。本研究利用机器学习与多组学数据的结合,开发了一种基于 EMT 相关基因的风险分层模型,旨在为 CRC 患者提供个性化的预后评估。我们利用公开的基因表达数据集来确定 EMT 相关基因,使用 CoxBoost 算法筛选这些基因以评估其预后意义。基于基因表达水平的模型在不同数据集上进行了严格的独立验证。我们的模型能够稳健地区分 CRC 患者的高风险和低风险类别,每个类别与明显不同的生存概率相关。值得注意的是,风险评分是 CRC 的一个独立预后指标。高风险患者的肿瘤微环境具有免疫抑制性,对某些化疗药物的反应性增强,这突显了该模型在指导靶向肿瘤治疗方面的潜力。此外,我们的研究揭示了长链非编码 RNA PVT1 与 EMT 相关基因 TIMP1 和 MMP1 之间可能存在抑制性相互作用,为 CRC 的分子复杂性提供了新的见解。总之,我们的研究引入了一种复杂的风险模型,利用机器学习和多组学的见解,准确预测 CRC 患者的预后,为更个体化和有效的肿瘤治疗模式铺平了道路。

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