Comprehensive machine learning-based integration develops a novel prognostic model for glioblastoma

Qian Jiang, Xiawei Yang, Teng Deng, Jun Yan, Fangzhou Guo, Ligen Mo, Sanqi An, Qianrong Huang
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Abstract

In this study, we developed a new prognostic model for glioblastoma (GBM) based on an integrated machine learning algorithm. We used univariate Cox regression analysis to identify prognostic genes by combining six GBM cohorts. Based on the prognostic genes, 10 machine learning algorithms were integrated into 117 algorithm combinations, and the artificial intelligence prognostic signature (AIPS) with the greatest average C-index was chosen. The AIPS was compared with 10 previously published models by univariate Cox analysis and the C-index. We compared the differences in prognosis, tumor immune microenvironment (TIME), and immunotherapy sensitivity between the high and low AIPS score groups. The AIPS based on the random survival forest algorithm with the highest average C-index (0.868) was selected. Compared with the previous 10 prognostic models, our AIPS has the highest C-index. The AIPS was closely linked to the clinical features of GBM. We discovered that patients in the low score group had improved prognoses, a more active TIME, and were more sensitive to immunotherapy. Finally, we verified the expression of several key genes by western blotting and immunohistochemistry. We identified an ideal prognostic signature for GBM, which might provide new insights into stratified treatment approaches for GBM patients.
基于机器学习的综合集成开发出胶质母细胞瘤的新型预后模型
在这项研究中,我们基于一种集成的机器学习算法开发了一种新的胶质母细胞瘤(GBM)预后模型。我们使用单变量 Cox 回归分析,结合六个 GBM 队列确定了预后基因。根据预后基因,将 10 种机器学习算法整合为 117 种算法组合,并选择了平均 C 指数最大的人工智能预后特征(AIPS)。通过单变量 Cox 分析和 C 指数,将 AIPS 与之前发表的 10 个模型进行了比较。我们比较了 AIPS 高分组和低分组在预后、肿瘤免疫微环境(TIME)和免疫疗法敏感性方面的差异。我们选择了平均 C 指数(0.868)最高的基于随机生存森林算法的 AIPS。与之前的 10 个预后模型相比,我们的 AIPS 具有最高的 C 指数。AIPS 与 GBM 的临床特征密切相关。我们发现,低分组患者的预后更好,TIME 更活跃,对免疫疗法更敏感。最后,我们通过免疫印迹和免疫组化验证了几个关键基因的表达。我们为 GBM 找出了一个理想的预后特征,这可能会为 GBM 患者的分层治疗方法提供新的见解。
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