基于上皮-间充质转化相关基因,利用机器学习和多组学方法构建结直肠癌个性化预后风险模型

IF 3.2 4区 医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Journal of Gene Medicine Pub Date : 2024-01-16 DOI:10.1002/jgm.3660
Shuze Zhang, Wanli Fan, Dong He
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引用次数: 0

摘要

结直肠癌(CRC)的进展和转移潜力与上皮-间质转化(EMT)过程密切相关。本研究利用机器学习的力量,结合多组学数据,建立了一个基于 EMT 相关基因的风险分层模型。目的是促进对 CRC 进行个性化预后评估。我们利用可公开访问的基因表达数据集来确定与 EMT 相关的基因,并采用 CoxBoost 算法来筛选这些具有预后意义的基因。根据基因表达水平建立的模型在各种数据集上进行了严格的独立验证。我们的模型显示出强大的能力,能将 CRC 患者分为不同的高风险和低风险类别,每个类别都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。高危患者的特点是肿瘤环境具有免疫抑制作用,对某些化疗药物的反应性更强,这凸显了该模型在指导定制化肿瘤疗法方面的潜力。此外,我们的研究还发现了长非编码 RNA PVT1 与 EMT 相关基因 TIMP1 和 MMP1 之间可能存在的抑制性相互作用,为了解 CRC 复杂的分子机制提供了新的视角。从本质上讲,我们的研究利用机器学习和多组学的洞察力引入了一个复杂的风险模型,它能准确预测 CRC 患者的预后,为更个体化、更有效的肿瘤治疗范例铺平了道路。
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Constructing a personalized prognostic risk model for colorectal cancer using machine learning and multi-omics approach based on epithelial–mesenchymal transition-related genes

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.

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来源期刊
Journal of Gene Medicine
Journal of Gene Medicine 医学-生物工程与应用微生物
CiteScore
6.40
自引率
0.00%
发文量
80
审稿时长
6-12 weeks
期刊介绍: The aims and scope of The Journal of Gene Medicine include cutting-edge science of gene transfer and its applications in gene and cell therapy, genome editing with precision nucleases, epigenetic modifications of host genome by small molecules, siRNA, microRNA and other noncoding RNAs as therapeutic gene-modulating agents or targets, biomarkers for precision medicine, and gene-based prognostic/diagnostic studies. Key areas of interest are the design of novel synthetic and viral vectors, novel therapeutic nucleic acids such as mRNA, modified microRNAs and siRNAs, antagomirs, aptamers, antisense and exon-skipping agents, refined genome editing tools using nucleic acid /protein combinations, physically or biologically targeted delivery and gene modulation, ex vivo or in vivo pharmacological studies including animal models, and human clinical trials. Papers presenting research into the mechanisms underlying transfer and action of gene medicines, the application of the new technologies for stem cell modification or nucleic acid based vaccines, the identification of new genetic or epigenetic variations as biomarkers to direct precision medicine, and the preclinical/clinical development of gene/expression signatures indicative of diagnosis or predictive of prognosis are also encouraged.
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