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全面分析肿瘤免疫中抗原呈递的相互作用和卵巢癌中 AIDPS 系统的建立。

Comprehensive analysis of the interaction of antigen presentation during anti-tumour immunity and establishment of AIDPS systems in ovarian cancer.

机构信息

Department of Obstetrics and Gynecology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.

Department of Pathology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.

出版信息

J Cell Mol Med. 2024 Apr;28(8):e18309. doi: 10.1111/jcmm.18309.

Abstract

There are hundreds of prognostic models for ovarian cancer. These genes are based on different gene classes, and there are many ways to construct the models. Therefore, this paper aims to build the most stable prognostic evaluation system known to date through 101 machine learning strategies. We combined 101 algorithm combinations with 10 machine learning algorithms to create antigen presentation-associated genetic markers (AIDPS) with outstanding precision and steady performance. The inclusive set of algorithms comprises the elastic network (Enet), Ridge, stepwise Cox, Lasso, generalized enhanced regression model (GBM), random survival forest (RSF), supervised principal component (SuperPC), Cox partial least squares regression (plsRcox), survival support vector machine (Survival-SVM). Then, in the train cohort, the prediction model was fitted using a leave-one cross-validation (LOOCV) technique, which involved 101 different possible combinations of prognostic genes. Seven validation data sets (GSE26193, GSE26712, GSE30161, GSE63885, GSE9891, GSE140082 and ICGC_OV_AU) were compared and analysed, and the C-index was calculated. Finally, we collected 32 published ovarian cancer prognostic models (including mRNA and lncRNA). All data sets and prognostic models were subjected to a univariate Cox regression analysis, and the C-index was calculated to demonstrate that the antigen presentation process should be the core criterion for evaluating ovarian cancer prognosis. In a univariate Cox regression analysis, 22 prognostic genes were identified based on the expression profiles of 283 genes involved in antigen presentation and the intersection of genes (p < 0.05). AIDPS were developed by our machine learning-based integration method, which was applied to these 22 genes. One hundred and one prediction models are fitted using the LOOCV framework, and the C-index is calculated for each model across all validation sets. Interestingly, RSF + Lasso was the best model overall since it had the greatest average C-index and the highest C-index of any combination of models tested on the validated data sets. In comparing external cohorts, we found that the C-index correlated AIDPS method using the RSF + Lasso method in 101 prediction models was in contrast to other features. Notably, AIDPS outperformed the vast majority of models across all data sets. Antigen-presenting anti-tumour immune pathways can be used as a representative gene set of ovarian cancer to track the prognosis of patients with cancer. The antigen-presenting model obtained by the RSF + Lasso method has the best C-INDEX, which plays a key role in developing antigen-presenting targeted drugs in ovarian cancer and improving the treatment outcome of patients.

摘要

有数百种卵巢癌预后模型。这些基因基于不同的基因类别,构建模型的方法也有很多。因此,本文旨在通过 101 种机器学习策略构建迄今为止最稳定的预后评估系统。我们将 101 种算法组合与 10 种机器学习算法相结合,创建了具有出色精度和稳定性能的抗原呈递相关遗传标记物 (AIDPS)。包含的算法集包括弹性网络 (Enet)、Ridge、逐步 Cox、Lasso、广义增强回归模型 (GBM)、随机生存森林 (RSF)、监督主成分 (SuperPC)、Cox 偏最小二乘回归 (plsRcox)、生存支持向量机 (Survival-SVM)。然后,在训练队列中,使用留一交叉验证 (LOOCV) 技术拟合预测模型,该技术涉及 101 种不同的预后基因组合。比较和分析了 7 个验证数据集 (GSE26193、GSE26712、GSE30161、GSE63885、GSE9891、GSE140082 和 ICGC_OV_AU),并计算了 C 指数。最后,我们收集了 32 个已发表的卵巢癌预后模型(包括 mRNA 和 lncRNA)。对所有数据集和预后模型进行单变量 Cox 回归分析,并计算 C 指数以证明抗原呈递过程应是评估卵巢癌预后的核心标准。在单变量 Cox 回归分析中,基于与抗原呈递相关的 283 个基因的表达谱和基因交集(p<0.05)确定了 22 个预后基因。通过我们基于机器学习的整合方法开发了 AIDPS,该方法应用于这 22 个基因。使用 LOOCV 框架拟合 101 个预测模型,并计算每个模型在所有验证集中的 C 指数。有趣的是,RSF+Lasso 是整体上最好的模型,因为它具有最大的平均 C 指数和在验证数据集中测试的任何模型组合的最高 C 指数。在比较外部队列时,我们发现使用 RSF+Lasso 方法的 AIDPS 方法的 C 指数与其他特征相关。值得注意的是,AIDPS 在所有数据集中的表现均优于绝大多数模型。抗原呈递抗肿瘤免疫途径可用作卵巢癌的代表性基因集,以跟踪癌症患者的预后。使用 RSF+Lasso 方法获得的抗原呈递模型具有最佳的 C-INDEX,这在开发卵巢癌抗原呈递靶向药物和改善患者治疗结果方面发挥着关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9079/11015395/bb824a15807d/JCMM-28-e18309-g001.jpg

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