Constructing a Prognostic Model for Subtypes of Colorectal Cancer Based on Machine Learning and Immune Infiltration-Related Genes

Yue Wen, Jing Liao, Chunyan Lu, Lan Huang, Yanling Ma
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Abstract

This study constructed a prognostic model combining machine learning-based immune infiltration-related genes in each CRC subtype. We used publicly accessible gene expression data and clinical information on colorectal cancer patients. Integrated bioinformatics analysis was used for the identification of immune-wise genes. Machine learning algorithms, like LASSO regression and random forest, were utilised to identify the most important genes that may serve as predictors for patient prognosis. Univariate Cox regression, consensus clustering as well as machine learning algorithms were conducted to construct a prognostic risk scoring model. Analysis of functional enrichment, immune infiltration analyses and copy number variations as well as mutational burdens was performed and validated at the single-cell level. A machine learning-based model is designed with good predictive power—an area under the receiver operating characteristic curve (AUC-ROC) of C-index in cross-validation. The model also achieved good calibration and discrimination ability to stratify patients into high- and low-risk groups with a statistically significant difference in OS (p < 0.05). We have integrated multiple types of gene network features into machine learning systems based on the characteristics of integrating networks with Multi-Expense Learning algorithms, and we propose a robust approach for predicting CRC molecular subtype patient survival. This model could potentially steer personalised treatment strategies and ameliorate outcomes in patients. Although validation in other cohorts and clinical situations is necessary, it may be useful.

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基于机器学习和免疫浸润相关基因构建结直肠癌亚型预后模型
本研究结合基于机器学习的免疫浸润相关基因构建了每个CRC亚型的预后模型。我们使用了可公开获取的结直肠癌患者的基因表达数据和临床信息。综合生物信息学分析用于免疫相关基因的鉴定。机器学习算法,如LASSO回归和随机森林,被用来识别可能作为患者预后预测因子的最重要基因。采用单变量Cox回归、共识聚类和机器学习算法构建预后风险评分模型。在单细胞水平上进行了功能富集分析、免疫浸润分析、拷贝数变化和突变负荷分析并进行了验证。设计了一个基于机器学习的模型,该模型具有良好的预测能力——交叉验证中c指数的受试者工作特征曲线下面积(AUC-ROC)。该模型也具有良好的校准和区分能力,将患者分为高危组和低危组,OS差异有统计学意义(p < 0.05)。我们将多种类型的基因网络特征集成到机器学习系统中,基于集成网络与多费用学习算法的特点,我们提出了一种预测CRC分子亚型患者生存的稳健方法。该模型可能会引导个性化治疗策略并改善患者的预后。虽然在其他队列和临床情况下验证是必要的,但它可能是有用的。
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期刊介绍: The Journal of Cellular and Molecular Medicine serves as a bridge between physiology and cellular medicine, as well as molecular biology and molecular therapeutics. With a 20-year history, the journal adopts an interdisciplinary approach to showcase innovative discoveries. It publishes research aimed at advancing the collective understanding of the cellular and molecular mechanisms underlying diseases. The journal emphasizes translational studies that translate this knowledge into therapeutic strategies. Being fully open access, the journal is accessible to all readers.
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