基于深度学习的头颈部鳞状细胞癌患者进展预测模型。
Deep learning-based model for predicting progression in patients with head and neck squamous cell carcinoma.
机构信息
Department of Otolaryngology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, China.
Department of Plastic Surgery, The 960th Hospital of the PLA Joint Logistic Support Force, Jinan, Shandong 250000, China.
出版信息
Cancer Biomark. 2020;27(1):19-28. doi: 10.3233/CBM-190380.
PURPOSE
This study endeavors to build a deep learning (DL)-based model for predicting disease progression in head and neck squamous cell carcinoma (HNSCC) patients by integrating multi-omics data.
METHODS
RNA sequencing, miRNA sequencing, and methylation data from The Cancer Genome Atlas (TCGA) were used as input for autoencoder, a DL approach. An autoencoder-based prognosis model for PFS was built by SVM algorithm and tested in three confirmation sets. Predictive performance of the model was compared to two alternative approaches. Differential expression analysis for mRNAs, microRNAs (miRNA) and methylation was conducted. Moreover, functional annotation of differentially expressed genes (DEGs) was achieved through function enrichment analysis.
RESULT
The DL-based prognosis model identified two subgroups of patients with significantly different PFS, and showcased a good model fitness (C-index = 0.73). The two identified PFS subtypes were successfully validated in three confirmation sets. The DL-based model was more accurate and efficient than principal component analysis (PCA) or individual Cox-PH-based models. There were 348 DEGs, 23 differentially expressed miRNAs and 55 differentially methylated genes between the two PFS subtypes. These genes were significantly involved in several immune-related biological processes and primary immunodeficiency, cell adhesion molecules (CAMs), B cell receptor signaling and leukocyte transendothelial migration pathways.
CONCLUSION
The DL-based model introduced in this study is reliable and robust in predicting disease progression in HNSCC patients. A number of pathways and genes targets are unraveled to be implicated in cancer progression. Utility of this model would facilitate development of more individualized therapy for HNSCC patients and improve prognosis.
目的
本研究旨在通过整合多组学数据,建立基于深度学习(DL)的头颈部鳞状细胞癌(HNSCC)患者疾病进展预测模型。
方法
使用来自癌症基因组图谱(TCGA)的 RNA 测序、miRNA 测序和甲基化数据作为自动编码器(DL 方法)的输入。通过 SVM 算法构建基于自动编码器的 PFS 预后模型,并在三个验证集中进行测试。将模型的预测性能与两种替代方法进行比较。对 mRNAs、microRNAs(miRNA)和甲基化进行差异表达分析。此外,通过功能富集分析实现差异表达基因(DEGs)的功能注释。
结果
基于 DL 的预后模型确定了两组具有显著不同 PFS 的患者,并且表现出良好的模型拟合度(C 指数=0.73)。两个鉴定的 PFS 亚型在三个验证集中均得到成功验证。与主成分分析(PCA)或单个 Cox-PH 模型相比,基于 DL 的模型更准确、更高效。在两种 PFS 亚型之间有 348 个 DEGs、23 个差异表达的 miRNA 和 55 个差异甲基化基因。这些基因显著参与了几个免疫相关的生物学过程和原发性免疫缺陷、细胞黏附分子(CAMs)、B 细胞受体信号和白细胞跨内皮迁移途径。
结论
本研究中引入的基于 DL 的模型在预测 HNSCC 患者疾病进展方面是可靠和稳健的。发现了一些途径和基因靶点与癌症进展有关。该模型的应用将有助于为 HNSCC 患者制定更个体化的治疗方案,改善预后。