Machine learning-based tumor-infiltrating immune cell-associated lncRNAs for predicting prognosis and immunotherapy response in patients with glioblastoma

基于机器学习的肿瘤浸润免疫细胞相关 lncRNA 用于预测胶质母细胞瘤患者的预后和免疫治疗反应

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作者:Hao Zhang, Nan Zhang, Wantao Wu, Ran Zhou, Shuyu Li, Zeyu Wang, Ziyu Dai, Liyang Zhang, Zaoqu Liu, Jian Zhang, Peng Luo, Zhixiong Liu, Quan Cheng

Abstract

Long noncoding ribonucleic acids (RNAs; lncRNAs) have been associated with cancer immunity regulation. However, the roles of immune cell-specific lncRNAs in glioblastoma (GBM) remain largely unknown. In this study, a novel computational framework was constructed to screen the tumor-infiltrating immune cell-associated lncRNAs (TIIClnc) for developing TIIClnc signature by integratively analyzing the transcriptome data of purified immune cells, GBM cell lines and bulk GBM tissues using six machine learning algorithms. As a result, TIIClnc signature could distinguish survival outcomes of GBM patients across four independent datasets, including the Xiangya in-house dataset, and more importantly, showed superior performance than 95 previously established signatures in gliomas. TIIClnc signature was revealed to be an indicator of the infiltration level of immune cells and predicted the response outcomes of immunotherapy. The positive correlation between TIIClnc signature and CD8, PD-1 and PD-L1 was verified in the Xiangya in-house dataset. As a newly demonstrated predictive biomarker, the TIIClnc signature enabled a more precise selection of the GBM population who would benefit from immunotherapy and should be validated and applied in the near future.

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